Panic Disder
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A Panic Attack involves the sudden onset of four or more of the following: 1) palpitations with a pounding heart or rapid heart beat, 2) sweating, 3) trembling or shaking 4) shortness of breath or smothering, 5) feeling of choking, 6) chest pain or discomfort, 7) nausea or abdominal distress, 8) dizziness, unsteady, lightheaded, or faint, 9) feelings of unreality or being detached from oneself, 10) fear of losing control or going crazy, 11) fear of dying, 12) numbness or tingling sensations, 13) chills or hot flushes.  

Panic Disorder consists of recurrent Panic Attacks over a period of at least one month with concern about more attacks or the consequences of the attacks.  Some Panic Disorders will be coupled with Agoraphobia, i.e. fear of being in places from which escape might be difficult.  Panic Disorder affects 1.5-3% of adults and usually starts in late teenage years up to the age of the mid-30s. Its intensity may wax and wane.  Most people improve with the simple passage of time, but even 10 years later more than half still have some symptoms. 

Genetic Anticipation Found: A study of 38 families with panic disorder found it occurring at an earlier age in later generations suggesting a role for trinucleotide repeat sequences as in myotonic dystrophy. Battaglia, Am J Psychiatry 5/98;155:590

Panic Disorder Often Associated with or Precedes Depression or Generalized Anxiety: Using Composite International Diagnostic Interview (CIDI) DSM-IV diagnoses from a stratified multi-stage population survey of 10,641 Australian adults, people who experienced panic attacks more than 12 months ago were 4 times more likely to have a Depressive Disorder. Those with panic attacks in the past 12 months were 13.3 times more likely to report current Depressive Disorders. Non-panic Anxiety Disorders were also markedly increased (OR=7.5 for lifetime, but not 12-month panic attacks, and 21.46 for 12-month panic attacks) and for Substance Use Disorders (2.1 and 4.6, respectively). Panic attacks as risk markers for mental disorders. Baillie AJ, Rapee RM. Macquarie University, Sydney, Australia. Soc Psychiatry Psychiatr Epidemiol. 2005 Mar;40(3):240-4.

May Be Partial Seizure: 3 pts rx 3 yr for panic really partial seizures. 68 yo man 4 yr 10-14 stereotypical attacks QD x 1-4 min pale, sweaty, agitated, tearful. 30yo woman 10 yr stereotypic pain in head, hyperventilating, palpitations x 15-30min up to 15/wk with husband noting swallowing and chewing during episodes. 47yo woman 3 yr 1-2 min breathless, claustrophobic, tearful, needing to go outside, flushed, sweaty, trembling, not responding appropriately. All had negative EEGs and 24 hr eeGs. Video EEG telemetry in 2 and MRI sclerosis L hippocampus found in 1 pt for Dx. Anti-epileptics 50% decr in 2 and 90% in one. Thompson S, Duncan J, Smith S: Partial seizures presenting as panic attacks. BMJ 00;321:1002-3

Buspirone = Placebo for Panic: DB PC 52 panic patients rx imipramine, buspirone, or placebo. Is buspirone effective for panic disorder? Sheehan DV, Raj AB, Sheehan KH, Soto S. J Clin Psychopharmacol 1990 Feb;10(1):3-11

Citalopram Helps: Celexa SSRI 20-60 mg/d helps in placebo DB 8 week of 475 pt with 279 then long-term. 20-30 mg/d best. Imipramine standard Rx. Tho one meta-analysis claims SSRIs better. Paroxetine found long-term benefit at minimum of 40 mg/d. Citalopram reported to have antiobsessive and antidepressive effects with one DB 8 wk study finding equal to clomipramine. This study citalopram 20-30 appears possibly superior to clomipramine. Ulla Lepola, U Helsinki, J Clin Psychiatry 10/98 59:528-34.

Exercise Helps But Clomipramine Better: DB PC study 10 weeks for 46 mod to severe panic disorder with or without agoraphobia found exercise achieved about 60-70% of the advantage over placebo that clomipramine did altho it had a 31% dropout rate vs 0% for the med. Broocks, Am J Psychiatry 5/98;155:603

Gabapentin No Clear Benefit: DB PC 103 patients. 600-3600mg/d. No difference vs. placebo. Pande, J Clin Psychoph 00;20:467

Genetics: Panic Disorder Gene Study: Example of Genetic Array Testing: In a study of 127 patients with Panic Disorder and 146 healthy adults using Arrayed Primer Extension technology, researchers genotyped 90 single nucleotide polymorphisms in 21 candidate genes of serotonin, cholecystokinin, dopamine and opioid neurotransmitter systems. Eight single nucleotide polymorphism markers in eight genes displayed at least a nominal association with any of the studied PD phenotype subgroups. Several polymorphisms of cholecystokinin, serotonin and dopamine systems were associated with PD-all and/or PD-comorbid phenotypes, while pure PD was associated only with HTR2A receptor 102T-C (P=0.01) and DRD1 receptor -94G-A (P=0.02) polymorphisms. Haplotype analysis supported an association of the cholecystokinin gene TG haplotype with the PD-all group (P=0.04), whereas DRD1 receptor CAA and HTR2A receptor AT haplotypes were associated with a lower risk for PD-pure phenotype (P=0.03 and P=0.04, respectively). Association study of 90 candidate gene polymorphisms in panic disorder. Maron E, Nikopensius T, et al. University of Tartu, Estonia. Psychiatr Genet. 2005 Mar;15(1):17-24.  Ed: While this type of testing is totally useless at present for clinical practice because no studies exist telling physicians what to do with the results, the incredible ability to simultaneously test for so many abnormalities will definitely affect future treatment.

Imipramine = CBT, but CBT Lasted Better: 312 pt DB PC, 9 months with treatment and 6 more months f/u. Imipramine as good as CBT at 3 and 9 months, but at 15 months, 25-41% with CBT, 20% with imipramine, 13% placebo. JAMA 00;283:2529, Barlow, Boston U

Imipramine > Trazodone: 74 pt DB imipramine, alprazolam,or trazonoe. Trazodone, which has serotonergic activity poorly tolerated. Alprazolam max benefit first week while benefit of imipramine built gradually through at least 8 weeks. Charney, Yale, J Clin Psychiatry 86;47:580

Inositol Helps Depr, OCD, Panic: DB PC studies found no benefit schiz, Alz, ADHD, autism but did find benefit for 12g/d for 4 weeks for 28 depr pts, for 12g/d for 21 panic patients, and 18g/d for 13 OCD patients. Minimal S-E. Levine, Ben Gurion U, Eur Neuropharm 97;7:147

Inositol = or Better Than Fluvoxamine: DB 18g/d vs up to 150mg/d. 20 18-65yos DSM-IV panic crossover study 4 weeks each condition. Equally effective tho inositol somewhat superior in first 4 weeks. Fewer side-effects with inositol tho 8 with nausea (16 fluvoxamine nausea). Palatnik A, Frolov K, Fux M, Benjamin J: Double-blind, controlled, crossover trial of inopsitol versus fluvoxamine for the treatment of panic disorder. J Clin Psychopharmacol 2001 Jun;21(3):335-9, Israel.

Magnesium Defiency Said Linked to Mitral Valve Prolapse: Idiopathic mitral valve prolapse (IMVP) refers to the systolic displacement of one or both mitral leaflets into the left atrium, with or without mitral regurgitation. It is one of the most common forms of cardiac abnormalities among young people, especially in women. IMVP usually appears to be a benign condition and even capable of recovery. Some studies suggest a link to causing Panic Disorder. Magnesium deficiency may cause abnormal fibrosis, abnormalities in collagen synthesis as well as in the myocardium, capable of inducing mitral apparatus dyskinesia. It is a part of a picture of metabolic abnormalities, alteration of immune and autonomic nervous systems, cardiac arrhythmias and thromboembolic phenomena in IMVP. Mg therapy is essential and specific for IMVP. In the majority of cases MD is due to Mg depletion and the oral Mg supplementation must be combined with Mg-sparing diuretics or physiological doses of vitamin D. Magnes Res. 2005 Mar;18(1):35-52. The importance of magnesium status in the pathophysiology of mitral valve prolapse. Bobkowski W, et al. Poznan University, Poland. 

Mirtazapine = Fluoxetine: Braz J Med Biol Res 2001 Oct;34(10):1303-7. 22 pt DB 8 weeks. Wt gain in 50% mirtaz v 7% fluox.

Paroxetine Helps Panic in DB: 278 pt 2 week washout 10 weeks rx 10, 20, or 40mg/d DB PC. 40 mg/d more effective than placebo but reduced attacks less than 50% however in the last 2 weeks, 86% on 40mg/d panic free vs 50% on placebo. Ballenger J, et al: Double-blind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorder. Am J Psyc 98;155:36-42. SmithKline Beecham

Propranolol No Benefit: DB PC 54 pt. Alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks. 5 week. USC. Munjack DJ, Crocker B, Cabe D, Brown R, Usigli R, Zulueta A, McManus M, McDowell D, Palmer R, Leonard M. J Clin Psychopharmacol 1989 Feb;9(1):22-7

Sertraline Helps Tho Placebo Did Very Well: 176 with panic with or without agoraphobia Rx 10 wk DB 50-200mg/d vs placebo. 80% decr in panic with sertraline v 60% with placebo. Diarrhea and tremor and some insomnia and fatigue. Arch Gen Psychiatry Mark Pollack, Mass Gen, 55:1010-16 11/98; Same in Am J Psychiatry 98; Pohl, Wayne State, 168 pt same protocol. 88% decr panic attack with med vs 53% with placebo. 9% term due to S-E. Four DB studies with fluvoxamine vs placebo, two with paroxetine vs placebo. Author claims tricyclic freq not tolerated and SSRIs "few of these potential adverse effects."

SSRI=TCA: Meta-analysis 43 studies no diff SSRI v TCA for effect on decreasing panic, agoraphobic avoidance, depression orgen. anxiety in panic disorder but drop out rate 18% v 31%. Acta Psy Scan 02;106:163-7

Panic Disorder: 5-HTP Might Help Panic Attacks: In a small DB PC study of 32 volunteers given a drug that induces panic attacks ( cholecystokinin-tetrapeptide (CCK-4)), 200 mg of 5-HTP given 90 minutes before the CCK-4 showed a nonsignificant reduction in panic rate (19% after 5-HTP and 44% after placebo, p = 0.13) with a trend for lower intensity of symptoms after 5-HTP (p = 0.08). The effect of 5-hydroxytryptophan on cholecystokinin-4-induced panic attacks in healthy volunteers. Maron E, Toru I, Vasar V, Shlik J. University of Tartu, Estonia. J Psychopharmacol. 2004 Jun;18(2):194-9

Panic Disorder: 5-HTP Helped Panic Patients in Experiment: The reaction of 24 panic disorder patients and 24 healthy volunteers to a 35% carbon dioxide panic challenge was assessed following administration of 200-mg of 5-HTP or placebo. L-5-Hydroxytryptophan significantly reduced the reaction to the panic challenge in panic disorder patients, regarding subjective anxiety, panic symptom score and number of panic attacks, as opposed to placebo. No such effect was observed in the healthy volunteers. Acute L-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients. Schruers K, van Diest R, Overbeek T, Griez E. Maastricht University, The Netherlands. Psychiatry Res. 2002 Dec 30;113(3):237-43