Optimising clinical management in panic disorder

Panic disorder (PD) is characterised by recurrent and predominantly unpredictable panic attacks that may occur with or without agoraphobia. Here we discuss the symptoms of PD, comorbid factors and neurological and genetic findings along with how best to screen for and treat PD.

Symptoms of PD

Around 300 million people worldwide are estimated to have an anxiety disorder, including panic disorder (PD), generalised anxiety disorder, social anxiety disorder and specific phobias.1 While lifetime prevalence of PD is 1−3%, it affects around 2.5 times more women than men.2 More recently, assessment of PD during the COVID-19 pandemic revealed that new incidence of PD was 3%, with predictive risk factors including stress experienced during the outbreak; a pre-existing mental disorder; geographical location; fear of infection; and perceived restrictiveness of containment measures.3

Panic episodes may involve fear symptoms, heart palpitations, feelings of choking and depersonalisation

PD is characterised by recurrent and predominantly unpredictable panic attacks that may occur with or without agoraphobia. Panic episodes/attacks may involve not only fear symptoms without apparent danger, such as fear of dying or losing control, but also physical symptoms, such as heart palpitations, chest pains or dyspnoea; feelings of choking, dizziness and faintness and of depersonalisation or derealisation. A person can be diagnosed with PD after as few as two panic attacks when accompanied by at least four of these symptoms. However, symptoms cannot be attributable to any other trigger, such as a response to a social situation, which would be classified as social anxiety disorder.4

 

Comorbidity

As mentioned, PD is associated with a number of physical symptoms thus high rates of comorbidity of PD and somatic disorders potentially cause difficulties in distinguishing a panic attack from symptoms of another cause.5 For instance, up to 25% of people with chronic obstructive pulmonary disease6 and 20% with asthma have comorbid PD.7 Cardiac disease symptoms have been reported to be associated with PD, for example, in one study 43% of emergency room patients reporting atypical chest pain had PD or a panic attack.8 Thyroid disorders have also been linked to the occurrence of PD9 and the occurrence of vestibular dysfunction symptoms such as dizziness and vertigo has been linked to high anxiety states.5

PD can be comorbid with somatic disorders such as asthma and psychiatric conditions such as major depressive disorder

There is high comorbidity of PD and other psychiatric disorders. For example, around 10% of people with major depressive disorder (MDD) and 20% of those with bipolar disorder also have PD and people with PD have a 47% increased risk of depression (94% when PD and social phobia are comorbid) and 7% increased risk of suicidality.5 There is also an increased risk of PD in people with an alcohol or drug use disorder, including nicotine dependence, any other anxiety disorder and personality disorders.10

 

Neurological and genetic findings in PD

Functional magnetic resonance imaging studies suggest that PD is associated with abnormal activities in the cortico-limbic network.11 This is comprised of the hippocampus and amygdala (involved with learning, memory and emotional stress) projecting to, and receiving signals from, the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (PFC) (involved in executive functions such as selective attention, motivation and social interactions).12

A review of studies examining processing of emotional facial expressions in people with PD found deficits in many cortico-limbic network regions compared to healthy controls, including both hyper- and hypo-activation patterns. This, the authors suggested, is reflected in knowledge of the ACC’s involvement in anticipatory anxiety and interoceptive hypervigilance; the PFC’s involvement in salience circuits to orient attention between external and internal stimuli; and the amygdala’s involvement in attentional-vigilance aspects of emotional stimuli processing and recognition of fearful and threatening stimuli and emotional and frightening facial expressions.11

In PD, deficits have been found in cortico-limbic network regions

PD is a polygenic disorder that has a high overlap with MDD, anxiety disorders, post-traumatic stress disorder and neuroticism.13 Studies examining the epigenetic factor of DNA methylation have found methylation differences in the regions of several genes in people with PD, including those involved in neurotransmitter transportation and processing. Moreover, a recent study found hypomethylation of a cytoskeleton-associated gene expressed in the amygdala, hippocampus, hypothalamus, cerebellum and cortical regions, which the authors proposed may have a role in neuronal function. This study also found methylation increases in a gene coding for an interleukin-1 alpha (IL-1a) and beta (IL-1b) receptor following 6 weeks of cognitive behavioural therapy (CBT), suggesting a role in anxiety of these cytokines that can be modulated by treatment.14

 

Screening for PD

Diagnostically, brief screening for PD can be carried out by first asking a person if they have sudden, unexpected, episodes of intense fear or discomfort. If they do, further questioning can include how many times they’ve had these episodes, if the worst part of the episode peaks within several minutes and whether the episode resulted in lasting fear of/worry about having another one, or consequences of such.15

A quick screen for PD can help assess whether a person may need more thorough investigation

A more comprehensive assessment can utilise the Panic and Agoraphobia Scale, a 13-item self-reported measure that can help assess severity and response of PD using 5-point rating scales.16,17 Another measure, the Panic Disorder Severity Scale (PDSS), can be delivered by a clinician or self-reported.16,18 The PDSS had seven items that assess various aspects of PD including distress during episodes; episode frequency; anticipatory anxiety; impairment/interference in social or work functioning; and agoraphobic and interoceptive fear and avoidance. These are rated on a scale of 0 (none) to 4 (severe), with a total score of 6−9 being slightly ill and ≥14 being markedly ill.18,19

 

Treatment for PD

Only around one-third of patients with PD seek treatment within a year of onset with many first going to medical specialists or emergency departments due to somatic symptoms.16 PD treatment centres around psychological and pharmaceutical therapies15,16 with considerations needed for patient preference, symptom severity and treatment availability, cost, tolerance and safety.16

Selective serotonin uptake inhibitors and serotonin-noradrenalin reuptake inhibitors are recommended as first-line pharmacotherapy.15,16,2022 Cognitive-behavioural therapy (CBT) and short-term psychodynamic therapy were found in a meta-analysis to be the best interventions for PD compared to treatment as usual.23 Another meta-analysis found that CBT delivered remotely can lead to large effect sizes on PD symptoms and are comparable to face-to-face CBT.24

Both pharmacotherapy and psychotherapy are guideline-recommended treatments for PD

Studies have found that the combination of pharmacotherapy and CBT may have benefits for some people with PD; however, guidelines suggest that treatment steps should be sequential to allow assessment of the effectiveness of the initial treatment first.15,16,2022

Educational financial support was provided by Otsuka Pharmaceuticals Europe Limited and H. Lundbeck A/S.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References

1. GBD 2019 Mental Disorders Collaborators. Lancet Psychiatry 2022; 9: 137−150.

2 Wittchen HU, et al. Eur Neuropsychopharmacol 2011; 21: 655−679.

3. Georgieva I, et al. Healthcare (Basel) 2021; 9: 664.

4. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Fifth edition. Panic Disorder: 300.01. American Psychiatric Association: USA, 2013.

5. Simon NM, Fischmann D. J Clin Psychiatry 2005; 66 Suppl 4: 8−15.

6. Porzelius J, et al. Behav Res Ther 1992; 30: 75−77.

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9. Simon NM, et al. J Affect Disord 2002; 69: 209−217.

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11. Oliva A, et al. J Affect Disord 2021; 282: 906−914.

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14. Ziegler C, et al. Transl Psychiatry 2019; 9: 314.

15. Katzman MA, et al. BMC Psychiatry 2014; 14 Suppl 1: S1.

16. Andrews G, et al. Aust N Z J Psychiatry 2018; 52: 1109−1172.

17. Bandelow B. Int Clin Psychopharmacol 1995; 10: 73−81.

18. Shear MK, et al. Am J Psychiatry 1997; 154: 1571−1575.

19. Furukawa TA, et al. Depress Anxiety 2009; 26: 922−929.

20. Baldwin DS, et al. J Psychopharmacol 2014; 28: 403−439.

21. Bandelow B, et al. World J Biol Psychiatry 2008; 9: 248−312.

22. Bandelow B, et al. Eur Arch Psychiatry Clin Neurosci 2021; Oct 5: 1−12.

23. Papola D, et al. Br J Psychiatry 2021; Oct 6: 1−13.

24. Efron G, Wootton BM. J Anxiety Disord 2021; 79: 102385.

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