Pharmacotherapy of panic disorder

Figures & data

Table 1 Selective serotonin reuptake inhibitors

Study	Design	n	Measures	Treatment	t	Results
Fluvoxamine
Black et al (1993)	Randomized comparison, placebo controlled	55	Number of patients free of panic attacks	Fluvoxamine vs cognitive therapy vs placebo	8 weeks	Fluvoxamine (57% of patients improved) > cognitive therapy (40%) > placebo (25%)
Hoehn-Saric et al (1993)	Double-blind, parallel-groups	50	Montgomery-Asberg Depression Scale, Clinical Anxiety Scale, Sheehan Disability Scale	Fluvoxamine vs placebo	8 weeks	Fluvoxamine > placebo
Bakish et al (1996)	Randomized, double-blind, placebo-controlled	54	Sheehan Scale, CGI	Fluvoxamine vs imipramine vs placebo		Fluvoxamine = imipramine > placebo
Asnis et al (2001)	Double-blind, placebo-controlled	188	Daily Panic Attack Inventory, Sheehan Disability Scale, Clinical Anxiety Scale, CGI	Fluvoxamine vs placebo	8 weeks	Fluvoxamine > placebo
Paroxetine
Oehrberg et al (1995)	Randomized, double-blind, placebo-controlled	#	Number of panic attacks	Paroxetine 20, 40, 60 mg vs placebo	12 weeks	Paroxetine > placebo (50% reduction in total number of panic attacks)
Ballenger et al (1998)	Double-blind, fixed-dose, placebo-controlled	278	Frequency of panic attacks	Paroxetine 10,20, 40 mg	10 weeks	40 mg (86% free of panic attacks)> 20 mg (65.2 %) > 10 mg (67.4 %) > placebo (50%)
Sheehan et al (2005)	Double-blind, placebo-controlled	889	% of patients panic-free, CGI, HAM-A, Marks Sheehab Phobia Scale, Sheehan Disability Scale	Paroxetine CR vs placebo	10 weeks	Paroxetine CR > placebo
Fluoxetine
Michelson et al (1998)	Randomized, placebo-controlled	243	Panic attack frequency, CGI, HAM-A, HAM-D, Sheehan Disability	Fluoxetine 10 mg vs fluoxetine 20 mg vs placebo	10 weeks	Fluoxetine > placebo
Michelson et al (2001)	Randomized, placebo-controlled	180	CGI-S, HAM-A, HAM-D, PDSS, Sheehan Disability	Fluoxetine vs placebo	12 weeks	FLuoxetine > placebo
Sertraline
Pollack et al (1998)	Randomized, double-blind, placebo-controlled	176	CGI-I, CGI-S, PDSS	Sertraline 50–200 mg vs placebo	10 weeks	Sertraline > placebo, p = 0.01
Londborg et al (1998)	Double-blind, placebo-controlled, fixed-dose	178	CGI-I, HAM-A	Sertraline 50,100,200 mg vs placebo	12 weeks	Sertraline 50 mg = 100 mg = 200 mg > placebo p = 0.01
Pohl et al (1998)	Randomized, double-blind. parallel-group, placebo-controlled	168	CGI-S, CGI-C	Sertraline vs placebo	10 weeks	Sertraline > placebo
Sheikh et al (2000)	Double-blind, randomized	322	HAM-D	Sertraline 50, 100, 200 mg vs placebo	12 weeks	Sertraline 50 = 100 = 200 mg > placebo
Bandelow et al (2004)	Double-blind, randomized	225	Panic and Agoraphobia Scale total score, CGI	Sertraline 50–150 mg vs paroxetine 40–60 mg	12 weeks	Sertraline = paroxetine, but sertraline better tolerated
Citalopram and escitalopram
Wade et al (2000)	Double-blind, placebo-controlled, parallel-group	475	Number of patients free of panic attacks	Clomipramine 60, 90 mg vs citalopram 10–60 mg vs placebo	8 weeks	Citalopram 20–30 mg > citalopram 40–60 mg
Stahl et al (2003)	Randomized, double-blind, placebo-controlled	366	Panic attack frequency, measured by Modified Sheehan Panic and Anticipatory Anxiety Scale, Panic and Agoraphobia Scale total score, CGI, Patient Global Evaluation, Quality of Life Enjoyment and Satisfaction Questionnaire	Escitalopram vs citalopram vs placebo	10 weeks	Both escitalopram and citalopram > placebo (p ≤ 0.05)

Abbreviations throughout tables: CBT, cognitive behavior therapy; CGI, CGI-C, CGI-S; HAM-A, Hamilton Rating Scale for Anxiety; HAM-D, Hamilton Rating Scale for Depression; DCS, D-cycloserine.

Table 2 Serotonin norepinephrine reuptake inhibitors

Study	Design	n	Measures	Treatment	t	Results
Pollack et al (1996)	Double-blind, placebo controlled	25	HAM-A, HAM-D	Venlafaxine vs placebo	8 weeks	Venlafaxine > placebo
Bradwejn et al (2005)	Double-blind, placebo-controlled	361	Proportion of patients free panic attacks, either full-symptom or reduced symptom	Venlafaxine ER 75–225 mg vs placebo	10 weeks	Venlafaxine ER > placebo in panic attack frequency and in the proportion free from limited-symptom panic attacks
Pollack et al (2007)	Double-blind, randomized, placebo-controlled	664	Percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale. Secondary measures: Panic Disorder Severity Scale, CGI-S, CGI-I	Venlafaxine ER 75, 150 mg vs paroxetine 40 mg vs placebo	12 weeks	Venlafaxine ER = paroxetine

Table 3 Long-term pharmacological treatment

Study	Design	n	Measures	Treatment	t	Results
Lecrubier et al (1997)	Double-blind, randomized, placebo-controlled	176	Daily panic attack diary, the CGI Scale, HAM-A, the Marks Sheehan Phobia Scale and the Sheehan Disability Scale	Paroxetine vs clomipramine vs placebo	48 weeks	Paroxetine = clomipramine > placebo. Paroxetine better tolerated
Lepola et al (1998)	Double-blind, parallel-group, placebo-controlled,	279	Physician’s Global Improvement Scale, the Patient’s Global Improvement Scale, HAM-A	Citalopram vs clomipraminevs placebo	1 year	Citalopram 20 or 30 mg/day > clomipramine > placebo (p < 0.05)
Michelson et al (1999)	Randomized	#	Panic attack frequency and phobia rating scale, HAM-A, HAM-D, SCL-90-R	Fluoxetine vs placebo	24 weeks	Fluoxetine significant amelioration, placebo significant worsening

Table 4 Sequential use of pharmacotherapy and CBT

Study	Design	n	Measures	Treatment	t	Results
Kampman et al (2002)	Next-step, randomized, double-blind, placebo-controlled	161	Agoraphobic behavior and anxiety discomfort	Manual-guided CBT of 15 sessions + paroxetine 40 mg/day or placebo	15 sessions	CBT + paroxetine > CBT + placebo p < 0.05
Heldt et al (2006)	Open next-step treatment study	63	CGI, Panic Inventory, HAM-A: baseline, 12th weekly session, 1-year post treatment	Existing various pharmacological treatment + 12 sessions of CBT	4 months	Reduction in both antidepressants and benzodiazepine use (p < 0.001) across treatment and follow-up

Figure 1 Virtual reality environments are presented using a head mounted display and tracking head movement.

Table 5 Cognitive enhancers and CBT

Study	Design	n	Measures	Treatment	t	Results
Ressler et al (2004)	Randomized, double-blind, placebo-controlled trial	28	Electrodermal skin fluctuation, acrophobia avoidance, acrophobia anxiety, attitudes toward heights, clinical global improvement, and number of self-exposures to real-world heights	2 sessions of behavioral exposure therapy + DCS vs placebo	3 months	CBT + DCS > CBT + placebo (p ≤ 0.05)
Hofmann et al (2006)	Randomized, double-blind, placebo-controlled augmentation trial	27	Social Phobia and Anxiety Inventory, Liebowitz Social Anxiety Scale Clinical, Global Impression Scale severity subscale	5 sessions exposure therapy + DCS vs placebo	1 month	D-cycloserine in addition to exposure therapy reported significantly less social anxiety compared with patients receiving exposure therapy plus placebo

Table 6 Primary care intervention

Study	Design	n	Measures	Treatment	t	Results
Rollman et al (2003)	randomized controlled	191	12-item Medical Outcomes Study Short Form, HAM-D	Telephone-based care management intervention vs usual care (notification of patient and physician)		Reduced anxiety (p ≤ 0.02) reduced depressive symptoms (p = 0.03); improved mental health-related quality of life (p = 0.01); and larger improvements relative to baseline in hours worked per week (p = 0.05) and fewer work days absent in the past month (p = 0.03) than usual care patients
Roy-Byrne et al (2005)	Randomized, controlled study comparing intervention to treatment as usual	232	% of subjects remitted (no panic attacks in the past month, minimal anticipatory anxiety, agoraphobia subscale score <10 on Fear Questionnaire) and responding (Anxiety Sensitivity Index score <20) and change over time in WHO Disability Scale and short form 12 scores	CBT + pharmacotherapy vs treatment as usual	12 months	CBT + pharmacotherapy > treatment as usual

BlackDWWesnerRBowersWA comparison of fluvoxamine, cognitive therapy, and placebo in the treatment of panic disorderArch Gen Psychiatry19935044508422221

 PubMed Web of Science ®Google Scholar

Hoehn-SaricRMcLeodDRHipsleyPAEffect of fluvoxamine on panic disorderJ Clin Psychopharmacology1993133216

 PubMed Web of Science ®Google Scholar

BakishDHooperCLFilteauMJA double-blind placebo-controlled trial comparing fluvoxamine and imipramine in the treatment of panic disorder with or without agoraphobiaPsychopharmacoly Bull19963213541

 PubMed Web of Science ®Google Scholar

AsnisGMHameediFAGoddardAWFluvoxamine in the treatment of panic disorder: a multi-center, double-blind, placebo-controlled study in outpatientsPsychiatry Res200110311411472786

 PubMed Web of Science ®Google Scholar

OehrbergSChristiansenPEBehnkeKParoxetine in the treatment of panic disorder. A randomised, double-blind, placebo-controlled studyBr J Psychiatry199516737497496647

 PubMed Web of Science ®Google Scholar

BallengerJCWheadonDESteinerMDouble-blind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorderAm J Psychiatry199815536429433336

 PubMed Web of Science ®Google Scholar

SheehanDVBurnhamDBIyengarMKEfficacy and tolerability of controlled-release paroxetine in the treatment of panic disorderJ Clin Psychiatry200566344015669886

 PubMed Web of Science ®Google Scholar

MichelsonDLydiardRBPollackMHOutcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study GroupAm J Psychiatry1998155157079812120

 PubMed Web of Science ®Google Scholar

MichelsonDAllgulanderCDantendorferKEfficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomised, placebo-controlled trialBr J Psychiatry2001179514811731354

 PubMed Web of Science ®Google Scholar

PollackMHOttoMWWorthingtonJJSertraline in the treatment of panic disorder: a flexible-dose multicenter trialArch Gen Psychiatry1998551010169819070

 PubMed Web of Science ®Google Scholar

LondborgPDWolkowRSmithWTSertraline in the treatment of panic disorder. A multi-site, double-blind, placebo-controlled, fixed-dose investigationBr J Psychiatry199817354609850204

 PubMed Web of Science ®Google Scholar

PohlRBWolkowRMClaryCMSertraline in the treatment of panic disorder: a double-blind multicenter trialAm J Psychiatry19981551189959734541

 PubMed Web of Science ®Google Scholar

SheikhJILondborgPClaryCMThe efficacy of sertraline in panic disorder: combined results from two fixed-dose studiesInt Clin Psychopharmacol2000153354211110009

 PubMed Web of Science ®Google Scholar

BandelowBBehnkeKLenoirSSertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparisonJ Clin Psychiatry2004654051315096081

 PubMed Web of Science ®Google Scholar

StahlSMGergelILiDEscitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trialJ Clin Psychiatry2003641322714658946

 PubMed Web of Science ®Google Scholar

PollackMHWorthingtonJJ3rdOttoMWVenlafaxine for panic disorder: results from a double-blind, placebo-controlled studyPsychopharmacol Bull199632667708993089

 PubMed Web of Science ®Google Scholar

BradwejnJAhokasASteinDJVenlafaxine extended-release capsules in panic disorder: flexible-dose, double-blind, placebo-controlled studyBr J Psychiatry2005187352916199795

 PubMed Web of Science ®Google Scholar

PollackMHLepolaUKoponenHA double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorderDepress Anxiety20072411416894619

 PubMed Web of Science ®Google Scholar

LecrubierYBakkerADunbarGA comparison of paroxetine, clomipramine and placebo in the treatment of panic disorder. Collaborative Paroxetine Panic Study InvestigatorsActa Psychiatr Scand199795145529065680

 PubMed Web of Science ®Google Scholar

LepolaUMWadeAGLeinonenEVA controlled, prospective, 1-year trial of citalopram in the treatment of panic disorderJ Clin Psychiatry199859528349818634

 PubMed Web of Science ®Google Scholar

MichelsonDPollackMLydiardRBContinuing treatment of panic disorder after acute response: randomised, placebo-controlled trial with fluoxetine. The Fluoxetine Panic Disorder Study GroupBr J Psychiatry1999174213810448445

 PubMed Web of Science ®Google Scholar

KampmanMKeijsersGPJHoogduinCALA randomized, double-blind, placebo-controlled study of the effects of adjunctive paroxetine in panic disorder patients unsuccessfully treated with cognitive-behavioural therapy aloneJ Clin Psychiatry200263772712363116

 PubMed Web of Science ®Google Scholar

HeldtEGus ManfroGKipperLOne-year follow-up of pharmacotherapy-resistant patients with panic disorder treated with cognitive-behavior therapy: Outcome and predictors of remissionBehav Res Therapy20064465765

 PubMed Web of Science ®Google Scholar

ResslerKJRothbaumBOTannenbaumLCognitive Enhancers as Adjuncts to Psychotherapy. Use of D-Cycloserine in Phobic Individuals to Facilitate Extinction of FearArch Gen Psychiatry20046111364415520361

 PubMed Web of Science ®Google Scholar

RollmanBLBelnapBHMazumdarSA randomized trial to improve the quality of treatment for panic and generalized anxiety disorders in primary careArch Gen Psychiatry20036213324116330721

 PubMed Web of Science ®Google Scholar

Roy-ByrnePPCraskeMGSteinMBA randomized effectiveness trial of cognitive-behavioural therapy and medication for primary care panic disorderArch Gen Psychiatry200562290815753242

 PubMed Web of Science ®Google Scholar