Journal Reading

PANIC DISORDER

Management of panic disorder

in primary care
Friska Ardiani Putri 201720401011154
Windy Kirtanti 201720401011096

Mentor: dr. Iwan Sys I., SpKJ

Department of Psychiatry
Faculty of Medicine Universitas Muhammadiyah Malang
2019
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 Introduction
• Recent epidemiological studies have suggested a lifetime prevalence in the
population of 13% for panic attacks and 2% for panic disorder in
accordance with Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) criteria.
• For GPs, knowledge of how to identify panic disorder and initiate one of
the many effective treatments is valuable, because if unrecognised, the
disorder has the potential not only to impair quality of life through its
disabling and unpleasant symptoms, but also to mimic several physical
illnesses exposing the patient to avoidable investigations and procedures.

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 • A panic attack is a discrete period of fear or
anxiety that has a rapid onset, reaches a
peak within 10 minutes and in which at
least four of 13 characteristic symptoms are
experienced.
• Many of these symptoms involve bodily
systems, such as racing heart, chest pain,
sweating, shaking, dizziness, flushing,
stomach churning, faintness,
breathlessness, numbness/tingling and
sensations of choking.

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 Risk factors and clinical course
Patients frequently have a family history of panic disorder or other
anxiety and mood disorders.

There is an association with “fearful spells” in childhood, and with

sexual or physical abuse.

Panic disorder typically develops in early adulthood, and it affects

about 2 to 3 percent of adults and adolescents. Women are twice as
likely as men to develop panic disorder.

Phobic symptoms commonly precede the panic attacks and onset

of panic disorder may be triggered by a life event or a period of
exposure to ongoing stress.

Smoking, alcoholism and respiratory disorders are further known

risk factors.

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 Panic disorder and other medical conditions

complicated and The somatic

requires careful symptoms of a
assessment. panic attack can
mimic a range of
conditions
including asthma,
congestive cardiac
failure, angina,
cardiac arrhythmia,
benign positional
vertigo and thyroid
abnormalities.

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Diagnostic features of panic disorder
(DSM-5)

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 TREATMENT OF PANIC DISORDER

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 Pharmacological Treatment
• Various medications have been shown to be effective against the symptoms
of panic disorder and clinical studies have demonstrated high rates of
effcacy – up to 80 per cent in some trials using drugs originally developed
for depressionm (antidepressants)
• In addition, several benzodiazepines were licensed as anxiolytics prior to
the emergence of panic disorder as a recognised diagnosis in 1980.
• The main classes with evidence of efficacy are drugs that augment the
function of serotonin (and sometimes noradrenaline) through reuptake
blockade and drugs acting as positive allosteric modulators at GABAA
receptor (benzodiazepines).

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 Drug Treatment Of Panic Attacks And
Panic Disorder As Indicated.
Acute panic attack Acute panic disorder Long-term panic disorder
Selective serotonin reuptake inhibitors (SSRIs)
Citalopram ✓ ✓
Escitalopram ✓
Fluoxetine ✓ ✓
Fluvoxamine ✓ ✓
Paroxetine ✓ ✓
Sertraline ✓ ✓*
Serotonin noradrenaline reuptake inhbitors (SNRIs)
Venlafaxine ✓ ✓

Tricyclic antidepressants
Clomipramine ✓ ✓
Imipramine ✓ ✓

Drugs in red are considered first-line treatments.

06/09/2019 Drug trials for acute treatment were double-blind with placebo control except where marked by the * symbol. 9
Trials for long-term treatment (six months – three years) are in most cases open follow-up phases of doubleblind trials
 Acute panic attack Acute panic disorder Long-term panic disorder

Other antidepressants
Phenelzine ✓
Moclobemide ✓* ✓*
Mirtazapine ✓*
Reboxetine ✓
Benzodiazepines
Alprazolam ✓ ✓ ✓
Clonazepam ✓ ✓
Diazepam ✓ ✓
Lorazepam ✓
Others
Gabapentin ✓
Risperidone ✓
Pindolol ✓
(as adjunct to
fluoxetine)
Sodium ✓
valproate

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 Comparison of attributes of SSRIs and
benzodiazepines in the treatment of panic disorder

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 Drug used in deppresion
• Given the various issues with benzodiazepines, the reuptake blocking drugs
that are familiar as treatments for depression, especially the selective
serotonin reuptake inhibitors (SSRIs) and the serotonin-noradrenaline
reuptake inhibitor (SNRI) venlafaxine, are generally considered to be the
preferred drug treatments in panic disorder. As with mood disorders, the
onset of clinical response typically occurs after at least two weeks.
• When prescribing any of the reuptake inhibitor drugs, it is wise either to
start with low doses and titrate upwards slowly.
• The most frequent longer term side-effects of SSRIs are
tiredness, weight gain, abdominal distress and sexual dysfunction.

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 Drug used in deppresan
• In recent years, regulatory bodies have highlighted evidence that citalopram
has been associated with a slightly elevated risk of QTc prolongation at
higher doses, which may indicate an increased risk of cardiac arrhythmia.
• Fluoxetine (CYP3A4 and CYP2D6), paroxetine (CYP2D6) and
fluvoxamine (CYP3A4 and CYP1A2) are all cytochrome P450 enzyme
inhibitors and hence increase the risk of drug interactions.
• A further step after SSRIs and/or venlafaxine is to switch to the
noradrenaline/serotonin-receptor blocking drug mirtazapine, which has
evidence of effectiveness in panic disorder derived from a randomised
comparator trial where it was as effective as fluoxetine.

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Beyond mirtazapine, the remaining antidepressant drugs with known efficacy
in panic disorder all belong to less widely used classes, which may not be as
familiar to the majority of prescribers.
• First, tricyclic antidepressants; clomipramine and imipramine.. These are
also serotonin and noradrenaline reuptake blockers, with additional
blockade of histamine, serotonin and acetyl choline receptors.
• Second, the selective noradrenergic reuptake inhibitor reboxetine has
proven effcacy although it too tends to provoke adverse effects similar to
the anticholinergic effects of tricyclic antidepressants.
• Third, there is also placebo-controlled RCT evidence for using the
monoamine oxidase inhibitor (MAOI) drug phenelzine and evidence from
comparator-controlled RCTs to support moclobemide, the reversible
inhibitor of monoamine oxidase.

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 Gabapentin and Pregabalin
• Gabapentin,  modulate glutamate neurotransmission  effective in
monotherapy,  for more severe cases.
• Evidence for gabapentin’s successor drug pregabalin is very limited 
inadequate to recommend pregabalin in non-co-morbid panic disorder.
• Several randomised trials  efficacy specifically in GAD and one in social
anxiety disorder  role to play where panic disorder and either GAD or
social anxiety disorder are present co-morbidly.

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 Antipsychotics
• Good-quality evidence for antipsychotic monotherapy is relatively sparse,
with only risperidone (a serotonin/dopaminereceptor blocker)
demonstrating equivalence to an SSRI in a randomised trial.

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 Benzodiazepines
• The benzodiazepines lorazepam, clonazepam, diazepam and alprazolam
also have evidence of efficacy for panic disorder in RCTs.
• Benzodiazepines have an advantage over other drugs of being able to
provide relief and remission more rapidly
• Most specialists are willing to prescribe benzodiazepines for short periods
for certain patients who have no history of substance misuse, especially
where the patient feels that the impact of their panic attacks is so great that
rapid relief is required.

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 Psychological treatments
• CBT : cognitive therapy and behavioural therapy,
– ‘third wave’ CBT techniques (which include mindfulness-based
approaches)
• Psychodynamic therapy
• Psychoeducation
• Supportive therapy.

– CBT  most extensive evidence base

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• Antidepressant medication + psychotherapy  superior efficacy over
psychotherapy alone and over antidepressants alone  acute treatment
phase and subsequent continuation phase.
• Psychotherapy alone (as well as combination treatment) preferable first-
line strategy to antidepressants alone
– Psychotherapy as the first-line treatment over antidepressants  should
be viewed with caution

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• Relapse rates 6–24 months after treatment discontinuation, ie stopping
antidepressants and/or ceasing psychotherapy sessions
– (a) patients who had been treated with the combination were less likely
than those who had received antidepressants to suffer relapse in this
period
– (b) no difference emerged between patients who had had the
combination and those who had received psychotherapy alone.

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 Conclusion
The preferred drug treatment strategy is to start with an SSRI antidepressant or the SNRI
venlafaxine.

If neither are successful  various classes of drugs used in depression that have randomised
trial evidence (including mirtazapine, reboxetine, certain tricylic antidepressants and
moclobemide), and other drugs with an evidence base such as gabapentin, risperidone,
pindolol augmentation of SSRIs and possibly sodium valproate.

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 Conclusion
Benzodiazepines are also effective, but controversional, have to decide as:
- Pro renata (when required; such as the ‘rescue medication’ approach)
- Regular but short-term prescription
- Occasionally as a longer-term regular prescription.

In addition, various psychotherapies, most notably CBT, but also supportive therapy and
psychodynamic therapy, have an established evidence base, and using psychotherapy
together with antidepressants may be more effective than either psychotherapy or
antidepressants alone.

Diagnosis and effective treatment is essential to prevent or reduce the many adverse
consequences of this potentially disabling anxiety disorder.

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 Thank You

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