Highlights & Basics
- Frequency of panic attacks may vary considerably in panic disorder, with some individuals reporting brief clusters of several panic episodes in a short period of time, weekly panic attacks, or periodic attacks over the course of several months.
- Higher risk among first-degree relatives; onset of attacks triggered by stress; often comorbid with other anxiety, mood, and substance-use disorders.
- Assessment is made through ruling out organic causes; self-report; clinical interview; and behavioral observation.
- Self-help, cognitive behavioral therapy, selective serotonin-reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are first-line treatments.
- Long-term management includes relapse prevention after treatment discontinuation.
Quick Reference
History & Exam
Key Factors
unexpected onset
apprehension and worry
behavioral avoidance
tachycardia
positive PRIME-MD panic screen
Panic Disorder Severity Scale (PDSS)
GAD-7 cut score ≥10
Other Factors
palpitations; chest pain and discomfort
nausea and abdominal pain
dizziness
perceptual abnormality
respiratory symptoms
reliance on safety cues
paresthesias
muscle shaking
sweating
fainting
chills or hot flushes
Diagnostics Tests
1st Tests to Order
clinical assessment
Other Tests to consider
ECG
blood glucose
thyroid function tests
metabolic panel
toxicology screen
Treatment Options
acute
acute panic attack
reassurance
ongoing
panic disorder
no comorbidity
with comorbid depression
with comorbid anxiety
Definition
Classifications
Diagnostic and statistical manual of mental disorders: 5th edition, text revision (DSM-5-TR)
- The experience of recurrent, unexpected panic attacks
- At least one of the attacks has been followed by a period of at least 1 month of one or both of the following: persistent concern or worry about additional panic attacks or their consequences (e.g., heart attack); a significant maladaptive change in behavior related to the attacks (e.g., avoidance of exercise or unfamiliar situations)
- Panic symptoms must not be attributable to substance-related effects (e.g., a drug of misuse, a medication), other medical conditions (e.g., hyperthyroidism, cardiopulmonary disorders), or other psychiatric disorders (e.g., social anxiety disorder, specific phobias, obsessive compulsive disorder, posttraumatic stress disorder, separation anxiety disorder).
Vignette
Common Vignette 1
Common Vignette 2
Other Presentations
Epidemiology
Etiology
- Genetic factors: the risk of panic disorder increases fivefold among first-degree relatives.[22] The concordance rates for monozygotic and dizygotic twins are approximately 23% and 6%, respectively, with meta-analytic findings attributing an estimated 30% to 50% of the variance to shared genetic liability.[22] [23] [24] Although identification of panic-specific genes has yielded inconclusive findings, it is likely that multiple genetic variants of small effect interact with each other and contribute to the panic disorder risk.[24] [25] One meta-analysis of candidate genes showed an association of panic disorder with TMEM132D gene variants.[26] One genome wide association study (GWAS) found that a polymorphism in the GLRB gene may predispose to panic disorder by increasing startle response and agoraphobic thoughts.[27] Epigenetic mechanisms are also believed to contribute to panic disorder predisposition, possibly by mediating gene-environment interactions.[28]
- Environmental factors: panic attacks, by definition, initially occur unexpectedly. However, they do happen in context, and thus certain features of the environment may become triggers that elicit intense anxiety symptoms. Significant histories of unpredictable and uncontrollable life stressors and trauma are common.[29] [30] Prior to the onset of panic attacks, up to 80% of patients report one or more major negative life events.[29] Asthma severity appears to be associated with an incremental risk for panic disorder.[5] Respiratory variability may also increase risk factor for later onset panic disorder.[31] Nicotine use and dependence are disproportionately high among patients with panic disorder, and may be temporally related to elevated risk for developing panic disorder.[6]
- Psychological factors: cognitive behavioral models of panic assume that repeated, unpleasant experiences with external (e.g., crowds) and internal (e.g., rapid heartbeat) triggers lead to selective attention and hypervigilance. In turn, individuals learn to catastrophically misinterpret normal physical symptoms as dangerous.[32] Across all anxiety disorders, there may be a perturbed threat response with abnormalities in the circuitry involved in attention, emotion, learning and memory.[33] Activation of the fight or flight response to perceived danger further amplifies the panic response, and attempts to manage the panic through escape, avoidance, and safety behaviors provide short-term relief but lead to increasing functional impairments across time.[34] Temperamental factors, such as behavioral inhibition, may contribute to panic risk in adulthood.[35] [36] Anxiety sensitivity, or a tendency to catastrophically misinterpret physical symptoms as dangerous, is viewed as a psychological risk factor for the development of panic disorder.[37] [38]
Pathophysiology
Diagnostic Approach
History/clinical interview
- Panic attacks are recurrent, with a history of occurring unexpectedly or "out of the blue," and peak within a few minutes.
- The focus of the fear or apprehension is on having another panic attack and/or the misinterpretation of the mental and physical consequences of the panic sensations as being dangerous.
- There may be avoidance or safety behaviors designed to minimize the experience of future panic episodes. Agoraphobia may also be a common consequence.
Behavioral observation
Physical exam
Laboratory tests
- Thyroid function tests
- Blood chemistries
- Complete blood count
- Blood glucose levels.
Screening tools
Risk Factors
History & Exam
Tests
Differential Diagnosis
Differentiating Signs/Symptoms
- Avoidance of at least 2 situations based upon fears that escape might be difficult.
- May experience panic sensations, but the panic sensations are expected as opposed to unexpected.
Differentiating Tests
- Structured clinical interview.
Specific phobia
Differentiating Signs/Symptoms
- Excessive or unrealistic fear of specific objects or situations. Identify precipitants for panic attacks; panic sensations are cued by anticipated or actual exposure to the phobic stimuli rather than unexpectedly. There may be absence of persistent concern or behavioral change because of fear of further panic attacks, unlike in panic disorder.
Differentiating Tests
- Structured clinical interview.
Social anxiety disorder
Differentiating Signs/Symptoms
- Focus of the fear involves concerns over being embarrassed and negatively evaluated by others. Identify precipitants for panic attacks; panic sensations are cued by anticipated and actual exposure to social and evaluative situations, rather than unexpectedly. There may be absence of persistent concern or behavioral change because of fear of further panic attacks, unlike in panic disorder.
Differentiating Tests
- Structured clinical interview.
Differentiating Signs/Symptoms
- In illness anxiety disorder patients are overly preoccupied with somatic symptoms and focus on their body. There may be a lack of autonomic hyperactivity. Fears are likely to be temporally more distant (e.g., cancer) compared to in panic disorder where fears are generally immediate (e.g., heart attack).
Differentiating Tests
- Structured clinical interview.
Posttraumatic stress disorder
Differentiating Signs/Symptoms
- Onset follows a potentially life-threatening stressor. Additional differential symptoms include emotional numbing and reexperiencing the trauma.
- Identify precipitants for panic attacks; panic sensations are cued by anticipated and actual exposure to trauma cues, rather than unexpectedly. There may be absence of persistent concern or behavioral change because of fear of further panic attacks, unlike in panic disorder.
Differentiating Tests
- Structured clinical interview.
Differentiating Signs/Symptoms
- Symptoms cued by perceived and actual separation from family members.
Differentiating Tests
- Structured clinical interview.
Differentiating Signs/Symptoms
- Symptoms caused by the direct physiologic effects of substance use or as a result of its withdrawal.
Differentiating Tests
- Structured clinical interview and toxicology screening.
Criteria
- Palpitations, pounding heart, or accelerated heart rate
- Sweating
- Trembling or shaking
- Sensations of shortness of breath or smothering
- Feelings of choking
- Chest pain or discomfort
- Nausea or abdominal distress
- Feeling dizzy, unsteady, light-headed or faint
- Chills or heat sensations
- Paresthesias (numbness or tingling sensations)
- Derealization (feelings of unreality) or depersonalization (being detached from oneself)
- Fears of losing control or "going crazy"
- Fear of dying.
Screening
Treatment Approach
General considerations
- Cognitive behavioral therapy (CBT)
- Medication
- The combination of CBT and medication.
Psychoeducation and lifestyle advice
- Good sleep
- Regular exercise
- Reduced use of caffeine, tobacco, and alcohol
- Healthy diet
- Staying engaged with meaningful activities and healthy social supports.
Panic attacks without panic disorder
Panic disorder with no comorbidity
- CBT is a time-limited, skills-based approach designed to modify thoughts, behaviors, and environmental contingencies that are maintaining or exacerbating symptoms and impairments, and is an effective first-line treatment.[94] [95] [96] [97] It may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. The evidence in favor of dCBT is growing, and it appears to be equally beneficial, compared with face-to-face CBT, for the management of panic disorder, with similar reductions in symptoms and improvements in quality of life.[85] [98] [99] [100] [101] [102] [103] [104] Therefore dCBT may be considered as an equal first-line option to face-to-face CBT.[4]
- Treatment sessions may continue for 12 to 14 visits, although 6 to 7 sessions have also been found to be effective.[105] A referral to a mental health professional with expertise in CBT is recommended. The referring physician and mental health professional should maintain routine collaboration. Evidence also suggests beneficial effects of collaborative care in primary care settings, including the use of computerized CBT and care coordination programs.[81] [84] [85] [106]
- The aim of cognitive behavioral therapy for panic is to enable the person to experience the symptoms of panic without feeling frightened, and also to eliminate reliance on avoidance and safety seeking in order to learn that nothing dangerous is actually going to happen during a panic attack. Temporarily increasing anxiety through facing feared sensations and situations in a predictable, controllable manner may often be necessary in order to learn how to self-manage and overcome panic.
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training (including breathing retraining), challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations. The latter involves exposure to both internal body sensations (as "behavioral experiments") and external triggers (if the individual also has agoraphobia). Exposure to relevant uncomfortable physical sensations (e.g., dizziness, hyperventilation, and tachycardia) in a gradual, repeated, controlled manner can reduce fearful beliefs and increase tolerance for these sensations over time. For example, the individual and the therapist may overbreathe together to demonstrate that this does not lead to loss of consciousness, or they may agree to exercise in a hot room to prove that a racing heart does not lead to a heart attack. External graded exposure involves gradually increasing the patient's tolerance to previously avoided situations (e.g., crowds, shops, queues, public transport) without relying on safety cues (e.g., spouse, medication). Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes. Although certain activities, such as exercise or drinking coffee, should be avoided during earlier stages of exposure therapy as they may provoke physical sensations similar to those experienced during panic episodes, these can be incorporated into the exposure hierarchy at later stages of treatment.
- dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- Self-help materials based on principles of CBT are beneficial. Bibliotherapy, either alone or in combination with brief phone contact, may be helpful in reducing panic-related symptoms.[88] [87] Self-help interventions yield a strong effect size, although therapist-administered treatment appears to outperform self-help.[91] Therapist-assisted exposure tends to result in greater reductions in agoraphobic avoidance and panic severity in comparison with those doing self-directed exposure without therapist assistance.[107] Bibliotherapy may be particularly helpful when used in combination with a professional who monitors treatment response.[89] The advantages of self-help interventions include cost, availability, ease of administration, and convenience. The disadvantages include the generic treatment approach, lack of accountability, and potential difficulties with understanding and properly implementing treatment principles.
- CBT adjunctive to pharmacotherapy may increase medication adherence, improve response rate, and reduce the amount of medication needed to gain symptom control.[95] [106] [108] [109] [110] [111] [112] [113] Patients discontinuing benzodiazepines may particularly benefit from adjunctive CBT.[114] [115]
- Also effective in the management of a variety of other symptoms, such as sleep disruption, and other disorders of anxiety and mood that commonly co-occur.[123]
- The choice of antidepressant depends on availability, adverse effects, risk of withdrawal symptoms (e.g., dizziness, irritability, nausea, rebound anxiety) and ease of titration. Paroxetine and venlafaxine have a higher risk of withdrawal symptoms than fluoxetine.
- Patients with anxiety disorders may be more susceptible to medication adverse effects; it is therefore advisable to start at the lowest dose and increase the dose with caution ("start low, go slow").[12]
- There is low-quality evidence suggesting that benzodiazepines are superior to placebo in the short-term management of panic disorder; data on the long term efficacy and risks of treatment are currently lacking, providing limited guidance for clinical practice.[131] Some clinicians consider benzodiazepines to be a useful part of the treatment armamentarium for a subsection of patients with anxiety disorders.[132] [133] However, their use within clinical practice is frequently limited due to concern about their associated adverse effects (e.g., cognitive impairment, falls, and sedation), tolerance, dependence, and potential for misuse.[4]
- Benzodiazepines are sometimes used for a short-term anxiety crisis, or as an adjunct to augment SSRIs, SNRIs, and TCAs in the management of patients with treatment-resistant panic disorder, or at the initiation of antidepressant therapy to prevent worsening of symptoms due to antidepressant side effects.[70] They are recommended for short-term use only (e.g., 2 to 4 weeks).[134]
- UK National Institute for Health and Care Excellence guidelines do not recommend using benzodiazepines for patients with panic disorder, stating that they are associated with less good outcomes in the long term.[69] However, other international practice guidelines recommend that cautious short-term benzodiazepine use may be considered as an alternative option for selected patients with panic disorders, for example for patients whose symptoms have not responded to other treatments or for management of severe agitation or anxiety during initiation of an SSRI.[4] [70]
- Tolerance, dependence, and misuse potential can be associated with all benzodiazepines. Short-acting agents may warrant special consideration of risks without demonstrating additional benefits.[135] [136] If benzodiazepines are indicated, the preference may be for scheduled, longer-acting agents so that medication use is time-dependent rather than response/panic-dependent. "As needed" use of short-acting benzodiazepines may result in the patient developing psychological dependence on these medications, which could diminish the ability for an individual to develop an internal locus of control over these symptoms, and so, if required, benzodiazepines should be dosed regularly and not "as needed".
- Avoid prescribing benzodiazepines for patients with a previous or current history of substance misuse.[4]
- They have a rapid onset of action and are generally well tolerated, although physiologic dependence can occur in as little as 2 to 4 weeks. Sedation and cognitive impairments can occur with use. Abrupt discontinuation or rapid tapering schedules can increase risk for withdrawal symptoms (e.g., dizziness, irritability, nausea, sweating, tremors, rebound anxiety, and seizure). Longer-acting agents (e.g., clonazepam) may be preferable to minimize interdose rebound anxiety.
- Long-term treatment with benzodiazepines should be rare, supervised, made with caution and based on careful consideration of the anticipated risks and benefits of benzodiazepines for the individual patient; specialist input (e.g., from a psychiatrist or addiction specialist) is advisable. Patients using benzodiazepines long-term should be regularly offered the opportunity to gradually withdraw from long-term use; treatment at the lowest effective dose is recommended.[134] [137]
- TCAs are indicated in patients for whom treatment with one or more SSRI has failed, or in patients with neuropathic pain. Patients with panic disorder with a high likelihood of pain complaints may also benefit from TCA treatment.[140]
- For an individual to develop an internal locus of control over these symptoms, and so, if required, benzodiazepines should be dosed regularly and not "as needed".
Panic disorder with comorbidity
- Patients are treated initially with CBT or SSRIs/SNRIs, or with TCAs where treatment with one or more SSRI/SNRI or CBT has failed. Benzodiazepines are relatively contraindicated for persons with comorbid depression.[123]
- Benzodiazepines are sometimes considered to be relatively contraindicated for persons with comorbid depression. However, there is moderate quality evidence that adding a benzodiazepine to an antidepressant regimen may be helpful towards improving depression severity, treatment response, and remission during the early phase of treatment. These benefits are not observed during acute and continuous phases.[142]
- Guidelines from the STAR*D study for treatment-resistant comorbid depression recommend dual pharmacotherapy in non-responding patients if they show a partial response (25% improvement in symptoms) with a maximum dose of 1 antidepressant.[143] Combining 2 drugs from groups with different mechanisms of action may be considered, the groups being SSRIs (paroxetine, sertraline, fluoxetine, fluvoxamine, citalopram, escitalopram), SNRIs (venlafaxine), mirtazapine, and TCAs (imipramine, clomipramine). Check carefully for drug interactions should be checked and consider consulting with a psychiatrist before initiating combination therapy.
- CBT for panic disorder is effective among patients with severe depression and/or comorbid substance use disorders.[144] Exposure-based CBT for panic disorder is effective in reducing anxiety and comorbid depressive symptoms, irrespective of depression severity.[145] Adjunctive CBT is also recommended for patients receiving pharmacotherapy.
- Treatment can be commenced with pharmacotherapy (i.e., SSRIs, SNRIs, benzodiazepines, TCAs) with or without CBT, or CBT alone. Benzodiazepines and TCAs are considered second-line pharmacotherapy.
Treatment duration and cessation
Treatment Options
acute panic attack
reassurance
Comments
- Provide reassurance that the symptoms are not dangerous and that the attack will subside soon.
- Patients usually hyperventilate as part of the attack but subjectively experience this as shortness of breath; this should be explained to the patient and an emphasis placed on slowing the breathing.
- Using a quiet room and support from a significant other are useful.
- In the emergency department setting, benzodiazepines may sometimes be considered to terminate an acute attack, for example if the patient's agitation or anxiety is particularly severe.[4]
panic disorder
no comorbidity
cognitive behavioral therapy (CBT)
Comments
- Treatment is individualized taking into account severity, potential adverse effects, past treatment history, patient preference, any comorbid disorders and treatment availability. As a general guide, for those with mild panic disorder, consider offering self-help or CBT alone initially. For those with panic disorder of moderate severity, consider offering CBT, an SSRI/SNRI, or a combination of CBT and medication. For those with severe panic disorder, consider offering both CBT and an SSRI/SNRI from the offset.[4]
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations. CBT can be used alone without pharmacotherapy, or may be used as an adjunct to any form of pharmacotherapy.[93]
- It is an effective first-line treatment.[95] [96] [97] Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153] Treatment sessions may continue for 12 to 14 visits, although 6 to 7 sessions have also been found to be effective.[105] A referral to a mental health professional with expertise in CBT is recommended. The referring physician and mental health professional should maintain routine collaboration. Evidence also suggests that CBT delivery is beneficial in primary care settings.[81] [106]
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient approach fear-provoking situations and sensations without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
SSRIs or SNRIs
Primary Options
- paroxetine
5-10 mg orally (immediate release) once daily initially, increase by 10 mg/day increments every 7 days according to response, maximum 60 mg/day
- paroxetine
- sertraline
25 mg orally once daily initially, increase by 25-50 mg/day increments every 7 days according to response, maximum 200 mg/day
- sertraline
- fluoxetine
5-10 mg orally (immediate release) once daily initially, increase by 10-20 mg/day increments every 4 weeks according to response, maximum 80 mg/day
- fluoxetine
- fluvoxamine
25-50 mg orally (immediate release) once daily initially, increase by 25-50 mg/day every 4-7 days according to response, maximum 300 mg/day
- fluvoxamine
- citalopram
5-10 mg orally once daily initially, increase by 10-20 mg/day increments every 7 days according to response, maximum 40 mg/day
- citalopram
- escitalopram
5 mg orally once daily initially, increase by 5-10 mg/day increments every 4 weeks according to response, maximum 20 mg/day
- escitalopram
- venlafaxine
37.5 mg orally (extended release) once daily initially, increase by 37.5 to 75 mg/day increments every 7 days according to response, maximum 225 mg/day
- venlafaxine
Comments
- Paroxetine is the least stimulating and most sedating of the SSRIs. Fluoxetine has a long half-life and therefore a lower risk of withdrawal symptoms, but it is more stimulating and requires slower titration.
- Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine are also effective.
- Patients with anxiety disorders may be more susceptible to medication adverse effects; it is therefore advisable to start at the lowest dose and increase the dose with caution ("start low, go slow").[12] Most adverse effects are time-limited during dose titration, and these should be discussed in advance with patients and monitored closely to ensure adherence.
psychoeducation and lifestyle advice
Comments
- Offer psychoeducation as soon as a diagnosis has been made.[12] A key part of any treatment approach is information and education about the nature of panic and anxiety. In particular, panic is an understandable reaction to perceived danger (the "fight or flight" response). Fear arises from the misinterpretation of normal body sensations. Drawing a simple diagram together with the person - linking symptoms, interpretation, anxiety with arrows in a "vicious circle" - can be helpful. It is important for the person to appreciate that the first goal of treatment is not to remove all anxiety, only to manage it successfully. Attempts by the person to cope (e.g., by avoidance or safety seeking) are understandable, but inadvertently lead to maintaining the problem.
- Advice on lifestyle factors includes: good sleep; regular exercise; reduced use of caffeine, tobacco, and alcohol; healthy diet; and staying engaged with meaningful activities and healthy social supports.[4]
cognitive behavioral therapy (CBT)
Comments
- Increased medication adherence and response rates, with a reduction in the amount of medication required to gain symptom control, are observed with adjunctive CBT.[93] [95] [106] [108] [109] [110] Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153]
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations.
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient stay in the feared situation long enough to allow fear reduction to occur without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
benzodiazepines
Primary Options
- clonazepam
0.25 mg orally twice daily initially, increase by 0.25 to 0.5 mg/day increments every 3 days according to response, maximum 4 mg/day
- clonazepam
Secondary Options
- alprazolam
0.25 to 0.5 mg orally (immediate release) four times daily initially, increase by 1 mg/day increments every 3-4 days according to response, maximum 6 mg/day
- alprazolam
- lorazepam
0.5 mg orally three times daily initially, increase gradually according to response, maximum 6 mg/day
- lorazepam
- diazepam
2.5 mg orally (immediate release) twice daily initially, increase gradually according to response, maximum 40 mg/day
- diazepam
Comments
- Benzodiazepines are not recommended for patients with panic disorder by some international guidelines, e.g., those from the UK National Institute for Health and Care Excellence, due to concerns about negative long-term outcomes.[69] However cautious short-term use of benzodiazepines is recommended by other guidelines as a second-line option for selected patients with panic disorders.[4] [70] Evidence on benzodiazepines for panic disorder are generally low in quality and cover short-term use only, providing limited guidance for clinical practice.[131]
- Benzodiazepines are recommended for short-term use only (e.g., 2 to 4 weeks).[134]
- If benzodiazepines are indicated, the preference may be for scheduled, longer-acting agents so that medication use is time-dependent rather than response/panic-dependent. "As needed" use of short-acting benzodiazepines may result in the patient developing psychological dependence on these medications, which could diminish the ability for an individual to develop an internal locus of control over these symptoms.
- Long-term treatment with benzodiazepines should be rare, supervised, made with caution and based on careful consideration of the anticipated risks and benefits of benzodiazepines for the individual patient; specialist input (e.g., from a psychiatrist or addiction specialist) is advisable. Patients using benzodiazepines long-term should be regularly offered the opportunity to gradually withdraw from long-term use; treatment at the lowest effective dose is recommended.[134] [137]
- Abrupt discontinuation or rapid tapering schedules can increase risk for withdrawal symptoms.
tricyclic antidepressants (TCAs)
Primary Options
- imipramine
10-25 mg orally once daily initially, increase by 10 mg/day increments every 2-4 days according to response, maximum 300 mg/day
- imipramine
- clomipramine
12.5 to 25 mg orally once daily initially, increase gradually according to response, maximum 250 mg/day
- clomipramine
Comments
- TCAs are indicated in patients for whom treatment with one or more selective serotonin-reuptake inhibitors (SSRIs) has failed, or in patients with neuropathic pain.
- They are less favorable with respect to adverse effects and may not be as well tolerated as SSRIs.[123]
- Serum imipramine levels may need to be monitored closely due to the relatively narrow therapeutic index.
psychoeducation and lifestyle advice
Comments
- Offer psychoeducation as soon as a diagnosis has been made.[12] A key part of any treatment approach is information and education about the nature of panic and anxiety. In particular, panic is an understandable reaction to perceived danger (the "fight or flight" response). Fear arises from the misinterpretation of normal body sensations. Drawing a simple diagram together with the person - linking symptoms, interpretation, anxiety with arrows in a "vicious circle" - can be helpful. It is important for the person to appreciate that the first goal of treatment is not to remove all anxiety, only to manage it successfully. Attempts by the person to cope (e.g., by avoidance or safety seeking) are understandable, but inadvertently lead to maintaining the problem.
- Advice on lifestyle factors includes: good sleep; regular exercise; reduced use of caffeine, tobacco, and alcohol; healthy diet; and staying engaged with meaningful activities and healthy social supports.[4]
cognitive behavioral therapy (CBT)
Comments
- Increased medication adherence and response rates, with a reduction in the amount of medication required to gain symptom control, are observed with adjunctive CBT.[93] [95] [106] [108] [109] [110] Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153]
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations.
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient stay in the feared situation long enough to allow fear reduction to occur without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
benzodiazepines
Primary Options
- clonazepam
0.25 mg orally twice daily initially, increase by 0.25 to 0.5 mg/day increments every 3 days according to response, maximum 4 mg/day
- clonazepam
Secondary Options
- alprazolam
0.25 to 0.5 mg orally (immediate release) four times daily initially, increase by 1 mg/day increments every 3-4 days according to response, maximum 6 mg/day
- alprazolam
- lorazepam
0.5 mg orally three times daily initially, increase gradually according to response, maximum 6 mg/day
- lorazepam
- diazepam
2.5 mg orally (immediate release) twice daily initially, increase gradually according to response, maximum 40 mg/day
- diazepam
Comments
- Some clinicians may consider offering benzodiazepine monotherapy to patients with panic disorder with a history of intolerance or poor response to antidepressants.
- Benzodiazepines are not recommended for panic disorder by some international guidelines, e.g., those from the UK National Institute for Health and Care Excellence, due to concerns about negative long-term outcomes.[69] However cautious short-term use of benzodiazepines is recommended by other guidelines as an alternative option for selected patients with panic disorders for example for patients whose symptoms have not responded to other treatments.[4] [70] Evidence on benzodiazepines for panic disorder are generally low in quality and cover short-term use only, providing limited guidance for clinical practice.[131] Benzodiazepines are recommended for short-term use only (e.g., 2 to 4 weeks).[134]
- If benzodiazepines are indicated, the preference may be for scheduled, longer-acting agents so that medication use is time-dependent rather than response/panic-dependent. "As needed" use of short-acting benzodiazepines may result in the patient developing psychological dependence on these medications, which could diminish the ability for an individual to develop an internal locus of control over these symptoms.
- Long-term treatment with benzodiazepines should be rare, supervised, made with caution and based on careful consideration of the anticipated risks and benefits of benzodiazepines for the individual patient; specialist input (e.g., from a psychiatrist or addiction specialist) is advisable. Patients using benzodiazepines long-term should be regularly offered the opportunity to gradually withdraw from long-term use; treatment at the lowest effective dose is recommended.[134] [137]
- Abrupt discontinuation or rapid tapering schedules can increase risk for withdrawal symptoms.
psychoeducation and lifestyle advice
Comments
- Offer psychoeducation as soon as a diagnosis has been made.[12] A key part of any treatment approach is information and education about the nature of panic and anxiety. In particular, panic is an understandable reaction to perceived danger (the "fight or flight" response). Fear arises from the misinterpretation of normal body sensations. Drawing a simple diagram together with the person - linking symptoms, interpretation, anxiety with arrows in a "vicious circle" - can be helpful. It is important for the person to appreciate that the first goal of treatment is not to remove all anxiety, only to manage it successfully. Attempts by the person to cope (e.g., by avoidance or safety seeking) are understandable, but inadvertently lead to maintaining the problem.
- Advice on lifestyle factors includes: good sleep; regular exercise; reduced use of caffeine, tobacco, and alcohol; healthy diet; and staying engaged with meaningful activities and healthy social supports.[4]
cognitive behavioral therapy (CBT)
Comments
- Increased medication adherence and response rates, with a reduction in the amount of medication required to gain symptom control, are observed with adjunctive CBT.[93] [95] [106] [108] [109] [110] Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153]
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations.
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient stay in the feared situation long enough to allow fear reduction to occur without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
with comorbid depression
cognitive behavioral therapy (CBT)
Comments
- CBT for panic disorder is effective among patients with severe depression and/or comorbid substance misuse.[144] Exposure-based CBT for panic disorder is effective in reducing anxiety and comorbid depressive symptoms, irrespective of depression severity.[145] Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153]
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations.
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient stay in the feared situation long enough to allow fear reduction to occur without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
SSRIs or SNRIs
Primary Options
- paroxetine
5-10 mg orally (immediate release) once daily initially, increase by 10 mg/day increments every 7 days according to response, maximum 60 mg/day
- paroxetine
- sertraline
25 mg orally once daily initially, increase by 25-50 mg/day increments every 7 days according to response, maximum 200 mg/day
- sertraline
- fluoxetine
5-10 mg orally (immediate release) once daily initially, increase by 10-20 mg/day increments every 4 weeks according to response, maximum 80 mg/day
- fluoxetine
- fluvoxamine
25-50 mg orally (immediate release) once daily initially, increase by 25-50 mg/day every 4-7 days according to response, maximum 300 mg/day
- fluvoxamine
- citalopram
5-10 mg orally once daily initially, increase by 10-20 mg/day increments every 7 days according to response, maximum 40 mg/day
- citalopram
- escitalopram
5 mg orally once daily initially, increase by 5-10 mg/day increments every 4 weeks according to response, maximum 20 mg/day
- escitalopram
- venlafaxine
37.5 mg orally (extended release) once daily initially, increase by 37.5 to 75 mg/day increments every 7 days according to response, maximum 225 mg/day
- venlafaxine
Comments
- Paroxetine is the least stimulating and most sedating of the SSRIs. Fluoxetine has a long half-life and therefore a lower risk of withdrawal symptoms, but it is more stimulating and requires slower titration.
- Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine are also effective.
- Patients with anxiety disorders may be more susceptible to medication adverse effects; it is therefore advisable to start at the lowest dose and increase the dose with caution ("start low, go slow").[12] Most adverse effects are time-limited during dose titration, and these should be discussed in advance with patients and monitored closely to ensure adherence.
psychoeducation and lifestyle advice
Comments
- Offer psychoeducation as soon as a diagnosis has been made.[12] A key part of any treatment approach is information and education about the nature of panic and anxiety. In particular, panic is an understandable reaction to perceived danger (the "fight or flight" response). Fear arises from the misinterpretation of normal body sensations. Drawing a simple diagram together with the person - linking symptoms, interpretation, anxiety with arrows in a "vicious circle" - can be helpful. It is important for the person to appreciate that the first goal of treatment is not to remove all anxiety, only to manage it successfully. Attempts by the person to cope (e.g., by avoidance or safety seeking) are understandable, but inadvertently lead to maintaining the problem.
- Advice on lifestyle factors includes: good sleep; regular exercise; reduced use of caffeine, tobacco, and alcohol; healthy diet; and staying engaged with meaningful activities and healthy social supports.[4]
cognitive behavioral therapy (CBT)
Comments
- Adjunctive CBT is also recommended for patients receiving pharmacotherapy.
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- Increased medication adherence and response rates, with a reduction in the amount of medication required to gain symptom control, are observed with adjunctive CBT.[95] [106] [108] [109] [110] Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations.
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient stay in the feared situation long enough to allow fear reduction to occur without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
tricyclic antidepressants (TCAs)
Primary Options
- imipramine
10-25 mg orally once daily initially, increase by 10 mg/day increments every 2-4 days according to response, maximum 300 mg/day
- imipramine
- clomipramine
12.5 to 25 mg orally once daily initially, increase gradually according to response, maximum 250 mg/day
- clomipramine
Comments
- TCAs are indicated in patients for whom treatment with one or more SSRI/SNRIs or CBT has failed, or in patients with neuropathic pain.
- They are less favorable with respect to adverse effects and may not be as well tolerated as SSRIs.[123]
- Serum imipramine levels may need to be monitored closely due to the relatively narrow therapeutic index.
psychoeducation and lifestyle advice
Comments
- Offer psychoeducation as soon as a diagnosis has been made.[12] A key part of any treatment approach is information and education about the nature of panic and anxiety. In particular, panic is an understandable reaction to perceived danger (the "fight or flight" response). Fear arises from the misinterpretation of normal body sensations. Drawing a simple diagram together with the person - linking symptoms, interpretation, anxiety with arrows in a "vicious circle" - can be helpful. It is important for the person to appreciate that the first goal of treatment is not to remove all anxiety, only to manage it successfully. Attempts by the person to cope (e.g., by avoidance or safety seeking) are understandable, but inadvertently lead to maintaining the problem.
- Advice on lifestyle factors includes: good sleep; regular exercise; reduced use of caffeine, tobacco, and alcohol; healthy diet; and staying engaged with meaningful activities and healthy social supports.[4]
cognitive behavioral therapy (CBT)
Comments
- Increased medication adherence and response rates, with a reduction in the amount of medication required to gain symptom control, are observed with adjunctive CBT.[95] [106] [108] [109] [110] Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153]
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations.
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient stay in the feared situation long enough to allow fear reduction to occur without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
dual pharmacotherapy
Primary Options
- paroxetine
5-10 mg orally (immediate release) once daily initially, increase by 10 mg/day increments every 7 days according to response, maximum 60 mg/day
or
- sertraline
25 mg orally once daily initially, increase by 25-50 mg/day increments every 7 days according to response, maximum 200 mg/day
or
- fluoxetine
5-10 mg orally (immediate release) once daily initially, increase by 10-20 mg/day increments every 4 weeks according to response, maximum 80 mg/day
or
- fluvoxamine
25-50 mg orally (immediate release) once daily initially, increase by 25-50 mg/day every 4-7 days according to response, maximum 300 mg/day
or
- citalopram
5-10 mg orally once daily initially, increase by 10-20 mg/day increments every 7 days according to response, maximum 40 mg/day
or
- escitalopram
5 mg orally once daily initially, increase by 5-10 mg/day increments every 4 weeks according to response, maximum 20 mg/day
AND
- venlafaxine
37.5 mg orally (extended release) once daily initially, increase by 37.5 to 75 mg/day increments every 7 days according to response, maximum 225 mg/day
- paroxetine
- paroxetine
5-10 mg orally (immediate release) once daily initially, increase by 10 mg/day increments every 7 days according to response, maximum 60 mg/day
or
- sertraline
25 mg orally once daily initially, increase by 25-50 mg/day increments every 7 days according to response, maximum 200 mg/day
or
- fluoxetine
5-10 mg orally (immediate release) once daily initially, increase by 10-20 mg/day increments every 4 weeks according to response, maximum 80 mg/day
or
- fluvoxamine
25-50 mg orally (immediate release) once daily initially, increase by 25-50 mg/day every 4-7 days according to response, maximum 300 mg/day
or
- citalopram
5-10 mg orally once daily initially, increase by 10-20 mg/day increments every 7 days according to response, maximum 40 mg/day
or
- escitalopram
5 mg orally once daily initially, increase by 5-10 mg/day increments every 4 weeks according to response, maximum 20 mg/day
AND
- mirtazapine
15 mg orally once daily initially, increase gradually according to response every 1-2 weeks, maximum 45 mg/day
- paroxetine
- paroxetine
5-10 mg orally (immediate release) once daily initially, increase by 10 mg/day increments every 7 days according to response, maximum 60 mg/day
or
- sertraline
25 mg orally once daily initially, increase by 25-50 mg/day increments every 7 days according to response, maximum 200 mg/day
or
- fluoxetine
5-10 mg orally (immediate release) once daily initially, increase by 10-20 mg/day increments every 4 weeks according to response, maximum 80 mg/day
or
- fluvoxamine
25-50 mg orally (immediate release) once daily initially, increase by 25-50 mg/day every 4-7 days according to response, maximum 300 mg/day
or
- citalopram
5-10 mg orally once daily initially, increase by 10-20 mg/day increments every 7 days according to response, maximum 40 mg/day
or
- escitalopram
5 mg orally once daily initially, increase by 5-10 mg/day increments every 4 weeks according to response, maximum 20 mg/day
AND
- imipramine
10-25 mg orally once daily initially, increase by 10 mg/day increments every 2-4 days according to response, maximum 300 mg/day
or
- clomipramine
12.5 to 25 mg orally once daily initially, increase gradually according to response, maximum 250 mg/day
- paroxetine
- venlafaxine
37.5 mg orally (extended release) once daily initially, increase by 37.5 to 75 mg/day increments every 7 days according to response, maximum 225 mg/day
and
- mirtazapine
15 mg orally once daily initially, increase gradually according to response every 1-2 weeks, maximum 45 mg/day
- venlafaxine
- venlafaxine
37.5 mg orally (extended release) once daily initially, increase by 37.5 to 75 mg/day increments every 7 days according to response, maximum 225 mg/day
AND
- imipramine
10-25 mg orally once daily initially, increase by 10 mg/day increments every 2-4 days according to response, maximum 300 mg/day
or
- clomipramine
12.5 to 25 mg orally once daily initially, increase gradually according to response, maximum 250 mg/day
- venlafaxine
- mirtazapine
15 mg orally once daily initially, increase gradually according to response every 1-2 weeks, maximum 45 mg/day
AND
- imipramine
10-25 mg orally once daily initially, increase by 10 mg/day increments every 2-4 days according to response, maximum 300 mg/day
or
- clomipramine
12.5 to 25 mg orally once daily initially, increase gradually according to response, maximum 250 mg/day
- mirtazapine
Comments
- Guidelines from the STAR*D study for treatment-resistant comorbid depression recommend dual pharmacotherapy in non-responding patients if they show a partial response (25% improvement in symptoms) with a maximum dose of 1 antidepressant.[143]
- Combining 2 drugs from groups with different mechanisms of action may be considered, the groups being selective serotonin-reuptake inhibitors (paroxetine, sertraline, fluoxetine, fluvoxamine, citalopram, escitalopram), serotonin-norepinephrine reuptake inhibitors (venlafaxine), mirtazapine, and tricyclic antidepressants (imipramine, clomipramine).
- Patients with anxiety disorders may be more susceptible to medication adverse effects; it is therefore advisable to start at the lowest dose and increase the dose with caution ("start low, go slow"). [12] Check carefully for drug interactions and consider consulting with a psychiatrist considered before initiating combination therapy.
psychoeducation/lifestyle advice
Comments
- Offer psychoeducation as soon as a diagnosis has been made.[12] A key part of any treatment approach is information and education about the nature of panic and anxiety. In particular, panic is an understandable reaction to perceived danger (the "fight or flight" response). Fear arises from the misinterpretation of normal body sensations. Drawing a simple diagram together with the person - linking symptoms, interpretation, anxiety with arrows in a "vicious circle" - can be helpful. It is important for the person to appreciate that the first goal of treatment is not to remove all anxiety, only to manage it successfully. Attempts by the person to cope (e.g., by avoidance or safety seeking) are understandable, but inadvertently lead to maintaining the problem.
- Advice on lifestyle factors includes: good sleep; regular exercise; reduced use of caffeine, tobacco, and alcohol; healthy diet; and staying engaged with meaningful activities and healthy social supports.[4]
cognitive behavioral therapy (CBT)
Comments
- Increased medication adherence and response rates, with a reduction in the amount of medication required to gain symptom control, are observed with adjunctive CBT.[95] [106] [108] [109] [110] Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153]
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations.
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient stay in the feared situation long enough to allow fear reduction to occur without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
with comorbid anxiety
cognitive behavioral therapy (CBT)
Comments
- Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153]
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations.
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient stay in the feared situation long enough to allow fear reduction to occur without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
SSRIs or SNRIs
Primary Options
- paroxetine
5-10 mg orally (immediate release) once daily initially, increase by 10 mg/day increments every 7 days according to response, maximum 60 mg/day
- paroxetine
- sertraline
25 mg orally once daily initially, increase by 25-50 mg/day increments every 7 days according to response, maximum 200 mg/day
- sertraline
- fluoxetine
5-10 mg orally (immediate release) once daily initially, increase by 10-20 mg/day increments every 4 weeks according to response, maximum 80 mg/day
- fluoxetine
- fluvoxamine
25-50 mg orally (immediate release) once daily initially, increase by 25-50 mg/day every 4-7 days according to response, maximum 300 mg/day
- fluvoxamine
- citalopram
5-10 mg orally once daily initially, increase by 10-20 mg/day increments every 7 days according to response, maximum 40 mg/day
- citalopram
- escitalopram
5 mg orally once daily initially, increase by 5-10 mg/day increments every 4 weeks according to response, maximum 20 mg/day
- escitalopram
- venlafaxine
37.5 mg orally (extended release) once daily initially, increase by 37.5 to 75 mg/day increments every 7 days according to response, maximum 225 mg/day
- venlafaxine
Comments
- Paroxetine is the least stimulating and most sedating of the SSRIs. Fluoxetine has a long half-life and therefore a lower risk of withdrawal symptoms, but it is more stimulating and requires slower titration.
- Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine are also effective.
- Patients with anxiety disorders may be more susceptible to medication adverse effects; it is therefore advisable to start at the lowest dose and increase the dose with caution ("start low, go slow").[12] Most adverse effects are time-limited during dose titration, and these should be discussed in advance with patients and monitored closely to ensure adherence.
psychoeducation and lifestyle advice
Comments
- Offer psychoeducation as soon as a diagnosis has been made.[12] A key part of any treatment approach is information and education about the nature of panic and anxiety. In particular, panic is an understandable reaction to perceived danger (the "fight or flight" response). Fear arises from the misinterpretation of normal body sensations. Drawing a simple diagram together with the person - linking symptoms, interpretation, anxiety with arrows in a "vicious circle" - can be helpful. It is important for the person to appreciate that the first goal of treatment is not to remove all anxiety, only to manage it successfully. Attempts by the person to cope (e.g., by avoidance or safety seeking) are understandable, but inadvertently lead to maintaining the problem.
- Advice on lifestyle factors includes: good sleep; regular exercise; reduced use of caffeine, tobacco, and alcohol; healthy diet; and staying engaged with meaningful activities and healthy social supports.[4]
cognitive behavioral therapy (CBT)
Comments
- Increased medication adherence and response rates, with a reduction in the amount of medication required to gain symptom control, are observed with adjunctive CBT.[95] [106] [108] [109] [110] Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153]
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations.
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient stay in the feared situation long enough to allow fear reduction to occur without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
benzodiazepines
Primary Options
- clonazepam
0.25 mg orally twice daily initially, increase by 0.25 to 0.5 mg/day increments every 3 days according to response, maximum 4 mg/day
- clonazepam
Secondary Options
- alprazolam
0.25 to 0.5 mg orally (immediate release) four times daily initially, increase by 1 mg/day increments every 3-4 days according to response, maximum 6 mg/day
- alprazolam
- lorazepam
0.5 mg orally three times daily initially, increase gradually according to response, maximum 6 mg/day
- lorazepam
- diazepam
2.5 mg orally (immediate release) twice daily initially, increase gradually according to response, maximum 40 mg/day
- diazepam
Comments
- Benzodiazepines are not recommended for patients with panic disorder by some international guidelines, e.g., those from the UK National Institute for Health and Care Excellence, due to concerns about negative long-term outcomes.[69] However cautious short-term use of benzodiazepines is recommended by other guidelines as an alternative option for selected patients with panic disorders, for example for patients whose symptoms have not responded to other treatments.[4] [70] Evidence on benzodiazepines for panic disorder are generally low in quality and cover short-term use only, providing limited guidance for clinical practice.[131]
- Benzodiazepines are recommended for short-term use only (e.g., 2 to 4 weeks).[134] Short-term benzodiazepines may be used for some patients as an adjunctive treatment to achieve a rapid reduction in panic attacks during the initial titration of a SSRI, for example if intense, persistent anxiety symptoms are interfering with treatment adherence and engagement, and if rapid control over anxiety symptoms is necessary.[4] [11] [70] [146] [154]
- If benzodiazepines are indicated, the preference may be for scheduled, longer-acting agents so that medication use is time-dependent rather than response/panic-dependent. "As needed" use of short-acting benzodiazepines may result in the patient developing psychological dependence on these medications, which could diminish the ability for an individual to develop an internal locus of control over these symptoms.
- Long-term treatment with benzodiazepines should be rare, supervised, made with caution and based on careful consideration of the anticipated risks and benefits of benzodiazepines for the individual patient; specialist input (e.g., from a psychiatrist or addiction specialist) is advisable. Patients using benzodiazepines long-term should be regularly offered the opportunity to gradually withdraw from long-term use; treatment at the lowest effective dose is recommended.[134] [137]
- Abrupt discontinuation or rapid tapering schedules can increase risk for withdrawal symptoms.
tricyclic antidepressants (TCAs)
Primary Options
- imipramine
10-25 mg orally once daily initially, increase by 10 mg/day increments every 2-4 days according to response, maximum 300 mg/day
- imipramine
- clomipramine
12.5 to 25 mg orally once daily initially, increase gradually according to response, maximum 250 mg/day
- clomipramine
Comments
- TCAs are indicated in patients for whom treatment with one or more SSRI/SNRIs or CBT has failed, or in patients with neuropathic pain.
- They are less favorable with respect to adverse effects and may not be as well tolerated as SSRIs.[123]
- Serum imipramine levels may need to be monitored closely due to the relatively narrow therapeutic index.
psychoeducation and lifestyle advice
Comments
- Offer psychoeducation as soon as a diagnosis has been made.[12] A key part of any treatment approach is information and education about the nature of panic and anxiety. In particular, panic is an understandable reaction to perceived danger (the "fight or flight" response). Fear arises from the misinterpretation of normal body sensations. Drawing a simple diagram together with the person - linking symptoms, interpretation, anxiety with arrows in a "vicious circle" - can be helpful. It is important for the person to appreciate that the first goal of treatment is not to remove all anxiety, only to manage it successfully. Attempts by the person to cope (e.g., by avoidance or safety seeking) are understandable, but inadvertently lead to maintaining the problem.
- Advice on lifestyle factors includes: good sleep; regular exercise; reduced use of caffeine, tobacco, and alcohol; healthy diet; and staying engaged with meaningful activities and healthy social supports.[4]
cognitive behavioral therapy (CBT)
Comments
- Increased medication adherence and response rates, with a reduction in the amount of medication required to gain symptom control, are observed with adjunctive CBT.[95] [106] [108] [109] [110] Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153]
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations.
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient stay in the feared situation long enough to allow fear reduction to occur without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
benzodiazepines
Primary Options
- clonazepam
0.25 mg orally twice daily initially, increase by 0.25 to 0.5 mg/day increments every 3 days according to response, maximum 4 mg/day
- clonazepam
Secondary Options
- alprazolam
0.25 to 0.5 mg orally (immediate release) four times daily initially, increase by 1 mg/day increments every 3-4 days according to response, maximum 6 mg/day
- alprazolam
- lorazepam
0.5 mg orally three times daily initially, increase gradually according to response, maximum 6 mg/day
- lorazepam
- diazepam
2.5 mg orally (immediate release) twice daily initially, increase gradually according to response, maximum 40 mg/day
- diazepam
Comments
- Some clinicians may consider offering benzodiazepine monotherapy to patients with panic disorder and comorbid anxiety with a history of intolerance to antidepressants. Benzodiazepines are not recommended for patients with panic disorder by some international guidelines, e.g., those from the UK National Institute for Health and Care Excellence, due to concerns about negative long-term outcomes.[69] However cautious short-term use of benzodiazepines is recommended by other guidelines as an alternative option for selected patients with panic disorders.[4] [70] Evidence on benzodiazepines for panic disorder are generally low in quality and cover short-term use only, providing limited guidance for clinical practice.[131] Benzodiazepines are recommended for short-term use only (e.g., 2 to 4 weeks).[134]
- If benzodiazepines are indicated, the preference may be for scheduled, longer-acting agents so that medication use is time-dependent rather than response/panic-dependent. "As needed" use of short-acting benzodiazepines may result in the patient developing psychological dependence on these medications, which could diminish the ability for an individual to develop an internal locus of control over these symptoms.
- Long-term treatment with benzodiazepines should be rare, supervised, made with caution and based on careful consideration of the anticipated risks and benefits of benzodiazepines for the individual patient; specialist input (e.g., from a psychiatrist or addiction specialist) is advisable. Patients using benzodiazepines long-term should be regularly offered the opportunity to gradually withdraw from long-term use; treatment at the lowest effective dose is recommended.[134] [137]
- Abrupt discontinuation or rapid tapering schedules can increase risk for withdrawal symptoms.
psychoeducation and lifestyle advice
Comments
- Offer psychoeducation as soon as a diagnosis has been made.[12] A key part of any treatment approach is information and education about the nature of panic and anxiety. In particular, panic is an understandable reaction to perceived danger (the "fight or flight" response). Fear arises from the misinterpretation of normal body sensations. Drawing a simple diagram together with the person - linking symptoms, interpretation, anxiety with arrows in a "vicious circle" - can be helpful. It is important for the person to appreciate that the first goal of treatment is not to remove all anxiety, only to manage it successfully. Attempts by the person to cope (e.g., by avoidance or safety seeking) are understandable, but inadvertently lead to maintaining the problem.
- Advice on lifestyle factors includes: good sleep; regular exercise; reduced use of caffeine, tobacco, and alcohol; healthy diet; and staying engaged with meaningful activities and healthy social supports.[4]
cognitive behavioral therapy (CBT)
Comments
- Increased medication adherence and response rates, with a reduction in the amount of medication required to gain symptom control, are observed with adjunctive CBT.[95] [106] [108] [109] [110] Patients with anxiety disorders (including panic disorder) who are treated with CBT experience significant improvements in symptoms during the 24 months following completion of treatment.[153]
- CBT may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. dCBT may be considered as an equal first-line option to face-to-face CBT.[4] dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
- CBT for panic disorder involves a combination of education, self-monitoring, relaxation training, challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations.
- Exposure therapy involves gradually increasing the patient's tolerance to previously avoided situations. The goal is to have the patient stay in the feared situation long enough to allow fear reduction to occur without engaging in escape or avoidance behavior or relying on safety cues. Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes.
panic attacks without panic disorder
counseling and monitoring
Comments
- Explain to patients that panic attacks affect up to one third of individuals in their lifetime but with less than 10% developing full panic disorder, and that although the attacks are uncomfortable, they are not dangerous and are time-limited.
- Encourage patients to monitor the intensity, frequency, and duration of attacks, and whether the episodes are expected or unexpected.
- Schedule a follow-up evaluation or a telephone check within 2 weeks to reassess the patient's symptoms. See above for recommended management of patients who then go on to meet DSM-5-TR criteria for panic disorder.
psychoeducation and lifestyle advice
Comments
- A key part of any treatment approach is information and education about the nature of panic and anxiety. In particular, panic is an understandable reaction to perceived danger (the "fight or flight" response). Fear arises from the misinterpretation of normal body sensations. Drawing a simple diagram together with the person - linking symptoms, interpretation, anxiety with arrows in a "vicious circle" - can be helpful. It is important for the person to appreciate that the first goal of treatment is not to remove all anxiety, only to manage it successfully. Attempts by the person to cope (e.g., by avoidance or safety seeking) are understandable, but inadvertently lead to maintaining the problem.
- Advice on lifestyle factors includes: good sleep; regular exercise; reduced use of caffeine, tobacco, and alcohol; healthy diet; and staying engaged with meaningful activities and healthy social supports.[4]
Emerging Tx
Brief cognitive behavioral therapy (CBT) interventions
Mental health apps
Anticonvulsants
Prevention
Primary Prevention
Follow-Up Overview
Prognosis
Monitoring
Complications
Citations
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Roy-Byrne P, Craske MG, Sullivan G, et al. Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial. JAMA. 2010 May 19;303(19):1921-8.[Abstract]
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Key Articles
Other Online Resources
Referenced Articles
Guidelines
Diagnostic
Summary
The USPSTF recommends screening for anxiety disorders in adults, including pregnant and postpartum persons. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for anxiety disorders in older adults.Published by
US Preventive Services Task Force
Published
2023
Summary
The USPSTF recommends screening for anxiety in children and adolescents ages 8 to 18 years. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for anxiety in children ages 7 years and younger.Published by
US Preventive Services Task Force
Published
2022
Summary
DSM-5-TR includes the fully revised text and references, updated diagnostic criteria and ICD-10-CM codes since DSM-5 was published in 2013.Published by
American Psychiatric Association
Published
2022
Summary
This evidence-based guideline summarizes key clinical features and screening instruments for the management of generalized anxiety disorder and panic disorder (with or without agoraphobia) in adults in primary, secondary, and community care.Published by
National Institute for Health and Care Excellence (UK)
Published
2020
Treatment
Summary
This evidence-based guideline summarizes cognitive behavioral therapy and medication management of patients with panic disorder, using DSM-5 criteria.Published by
Anxiety Disorders Association of Canada
Published
2014
Summary
This evidence-based guideline provides advice on care and treatment of adults with generalized anxiety disorder or panic disorder (with or without agoraphobia, using the specifiers in the DSM-IV-TR diagnostic criteria), including a step-wise approach to psychological and pharmacological interventions.Published by
National Institute for Health and Care Excellence (UK)
Published
2020
Summary
Practical clinical guidance for the treatment of adults with panic disorder, social anxiety disorder and generalised anxiety disorder in Australia and New Zealand.Published by
Royal Australian and New Zealand College of Psychiatrists
Published
2018