Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta‐analysis

We conducted a meta‐analysis of randomized trials in which the effects of treatment with antidepressant medication were compared to the effects of combined pharmacotherapy and psychotherapy in adults with a diagnosed depressive or anxiety disorder. A total of 52 studies (with 3,623 patients) met inclusion criteria, 32 on depressive disorders and 21 on anxiety disorders (one on both depressive and anxiety disorders). The overall difference between pharmacotherapy and combined treatment was Hedges' g = 0.43 (95% CI: 0.31‐0.56), indicating a moderately large effect and clinically meaningful difference in favor of combined treatment, which corresponds to a number needed to treat (NNT) of 4.20. There was sufficient evidence that combined treatment is superior for major depression, panic disorder, and obsessive‐compulsive disorder (OCD). The effects of combined treatment compared with placebo only were about twice as large as those of pharmacotherapy compared with placebo only, underscoring the clinical advantage of combined treatment. The results also suggest that the effects of pharmacotherapy and those of psychotherapy are largely independent from each other, with both contributing about equally to the effects of combined treatment. We conclude that combined treatment appears to be more effective than treatment with antidepressant medication alone in major depression, panic disorder, and OCD. These effects remain strong and significant up to two years after treatment. Monotherapy with psychotropic medication may not constitute optimal care for common mental disorders.

[1]  G. Andersson,et al.  The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: a meta‐analysis of direct comparisons , 2013, World psychiatry : official journal of the World Psychiatric Association.

[2]  H. Möller,et al.  Guidelines for the pharmacological treatment of anxiety disorders, obsessive–compulsive disorder and posttraumatic stress disorder in primary care , 2012, International journal of psychiatry in clinical practice.

[3]  Michelle G. Newman,et al.  Combined medication and cognitive therapy for generalized anxiety disorder. , 2011, Journal of anxiety disorders.

[4]  C. Chan,et al.  The Long-Term Effects of Psychotherapy Added to Pharmacotherapy on Morning to Evening Diurnal Cortisol Patterns in Outpatients with Major Depression , 2011, Psychotherapy and Psychosomatics.

[5]  M. Olfson,et al.  National trends in outpatient psychotherapy. , 2010, The American journal of psychiatry.

[6]  M. Olfson,et al.  National trends in the treatment for depression from 1998 to 2007. , 2010, Archives of general psychiatry.

[7]  Farooq Naeem,et al.  Preliminary Evaluation of Culturally Sensitive CBT for Depression in Pakistan: Findings from Developing Culturally-Sensitive CBT Project (DCCP) , 2010, Behavioural and Cognitive Psychotherapy.

[8]  Michele Tarsilla.  Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[9]  M. Atef-Vahid,et al.  Metacognitive Therapy (MCT), Fluvoxamine, and Combined Treatment in Improving Obsessive-Compulsive, Depressive and Anxiety Symptoms in Patients with Obsessive-Compulsive Disorder (OCD) , 2010 .

[10]  G. Maina,et al.  No Effect of Adding Brief Dynamic Therapy to Pharmacotherapy in the Treatment of Obsessive-Compulsive Disorder with Concurrent Major Depression , 2010, Psychotherapy and Psychosomatics.

[11]  Z. Segal,et al.  A randomized trial of sertraline, self-administered cognitive behavior therapy, and their combination for panic disorder , 2010, Psychological Medicine.

[12]  Gerhard Andersson,et al.  Efficacy of cognitive–behavioural therapy and other psychological treatments for adult depression: meta-analytic study of publication bias , 2010, British Journal of Psychiatry.

[13]  M. Liebowitz,et al.  A placebo-controlled trial of phenelzine, cognitive behavioral group therapy, and their combination for social anxiety disorder. , 2010, Archives of General Psychiatry.

[14]  Gerhard Andersson,et al.  Adding psychotherapy to pharmacotherapy in the treatment of depressive disorders in adults: a meta-analysis. , 2009, The Journal of clinical psychiatry.

[15]  K. Cain,et al.  Brief Psychosocial–Behavioral Intervention With Antidepressant Reduces Poststroke Depression Significantly More Than Usual Care With Antidepressant: Living Well With Stroke: Randomized, Controlled Trial , 2009, Stroke.

[16]  E. Schramm,et al.  [Interpersonal psychotherapy and pharmacotherapy for post-stroke depression. Feasibility and effectiveness]. , 2009, Der Nervenarzt.

[17]  E. Schramm,et al.  Interpersonelle Psychotherapie und Pharmakotherapie bei Post-Stroke-Depression , 2009, Der Nervenarzt.

[18]  G. Andersson,et al.  Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta‐analysis , 2009, Depression and anxiety.

[19]  M. Zarabian,et al.  Efficacy of Pharmacotherapy and Cognitive Therapy, alone and in Combination in Major Depressive Disorder , 2008, European Psychiatry.

[20]  Xiao-Hua Zhou,et al.  Statistical Methods for Meta‐Analysis , 2008 .

[21]  W. Hale,et al.  Is a combined therapy more effective than either CBT or SSRI alone? Results of a multicenter trial on panic disorder with or without agoraphobia , 2008, Acta psychiatrica Scandinavica.

[22]  R. Rosenthal,et al.  Selective publication of antidepressant trials and its influence on apparent efficacy. , 2008, The New England journal of medicine.

[23]  P. Spinhoven,et al.  Severity and duration of depression, not personality factors, predict short term outcome in the treatment of major depression. , 2007, Journal of affective disorders.

[24]  Nikolaos A Patsopoulos,et al.  Uncertainty in heterogeneity estimates in meta-analyses , 2007, BMJ : British Medical Journal.

[25]  M. Kozak,et al.  Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder. , 2007, The American journal of psychiatry.

[26]  J. Suvisaari,et al.  Impact of psychiatric disorders on health-related quality of life: general population survey , 2007, British Journal of Psychiatry.

[27]  N. Frasure-smith,et al.  Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. , 2007, JAMA.

[28]  N Watanabe,et al.  Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia. , 2007, The Cochrane database of systematic reviews.

[29]  Hans-Jürgen Möller,et al.  World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders in Primary Care , 2007, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[30]  R. Schoevers,et al.  Relative efficacy of psychotherapy and combined therapy in the treatment of depression: A meta-analysis , 2007, European Psychiatry.

[31]  P. Cuijpers,et al.  Costs of nine common mental disorders: implications for curative and preventive psychiatry. , 2006, The journal of mental health policy and economics.

[32]  C. Mathers,et al.  Projections of Global Mortality and Burden of Disease from 2002 to 2030 , 2006, PLoS medicine.

[33]  B. Rothbaum,et al.  Augmentation of sertraline with prolonged exposure in the treatment of posttraumatic stress disorder. , 2006, Journal of traumatic stress.

[34]  C. Dockery,et al.  Moclobemide and cognitive behavioral therapy in the treatment of social phobia. A six-month controlled study and 24 months follow up. , 2006, Neuro endocrinology letters.

[35]  David J. Kupfer,et al.  Size of Treatment Effects and Their Importance to Clinical Research and Practice , 2006, Biological Psychiatry.

[36]  S. Bellino,et al.  Combined Treatment of Major Depression in Patients with Borderline Personality Disorder: A Comparison with Pharmacotherapy , 2006, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[37]  Jasper A. J. Smits,et al.  Combined Psychotherapy and Pharmacotherapy for Mood and Anxiety Disorders in Adults: Review and Analysis , 2006 .

[38]  J. Markowitz,et al.  A comparative trial of psychotherapy and pharmacotherapy for "pure" dysthymic patients. , 2005, Journal of affective disorders.

[39]  H. Westenberg,et al.  Behavior therapy augments response of patients with obsessive-compulsive disorder responding to drug treatment. , 2005, The Journal of clinical psychiatry.

[40]  Olga V. Demler,et al.  Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. , 2005, Archives of general psychiatry.

[41]  H. Birnbaum,et al.  The economic burden of depression in the US: societal and patient perspectives , 2005, Expert opinion on pharmacotherapy.

[42]  K. Gadde,et al.  Fluoxetine, comprehensive cognitive behavioral therapy, and placebo in generalized social phobia. , 2004, Archives of general psychiatry.

[43]  Pratibha Reebye,et al.  The use of paroxetine and cognitive-behavioral therapy in postpartum depression and anxiety: a randomized controlled trial. , 2004, The Journal of clinical psychiatry.

[44]  G. Sachs,et al.  Personality disorder and social anxiety predict delayed response in drug and behavioral treatment of panic disorder. , 2004, Journal of affective disorders.

[45]  T. B. Üstün,et al.  Global burden of depressive disorders in the year 2000 , 2004, British Journal of Psychiatry.

[46]  G. Keitner,et al.  Combined Psychotherapy and Pharmacotherapy for the Treatment of Major Depressive Disorder , 2004 .

[47]  D. Hinton,et al.  Treatment of pharmacotherapy-refractory posttraumatic stress disorder among Cambodian refugees: a pilot study of combination treatment with cognitive-behavior therapy vs sertraline alone. , 2003, Behaviour research and therapy.

[48]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[49]  Olga V. Demler,et al.  The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). , 2003, JAMA.

[50]  A. Andreoli,et al.  Psychodynamic psychotherapy and clomipramine in the treatment of major depression. , 2002, Psychiatric services.

[51]  C. Byrne,et al.  Sertraline and/or interpersonal psychotherapy for patients with dysthymic disorder in primary care: 6-month comparison with longitudinal 2-year follow-up of effectiveness and costs. , 2002, Journal of affective disorders.

[52]  I. Holme,et al.  Randomised controlled general practice trial of sertraline, exposure therapy and combined treatment in generalised social phobia , 2001, British Journal of Psychiatry.

[53]  L. Thompson,et al.  Comparison of desipramine and cognitive/behavioral therapy in the treatment of elderly outpatients with mild-to-moderate depression. , 2001, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[54]  J. Dekker,et al.  Combining psychotherapy and antidepressants in the treatment of depression. , 2001, Journal of affective disorders.

[55]  Azhar Mz.  Comparison of Fluvoxamine alone, Fluvoxamine and cognitive psychotherapy and psychotherapy alone in the treatment of panic disorder in Kelantan--implications for management by family doctors. , 2000 .

[56]  S Duval,et al.  Trim and Fill: A Simple Funnel‐Plot–Based Method of Testing and Adjusting for Publication Bias in Meta‐Analysis , 2000, Biometrics.

[57]  J. Markowitz,et al.  A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. , 2000, The New England journal of medicine.

[58]  M K Shear,et al.  Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. , 2000, JAMA.

[59]  Fortunato Rizzo,et al.  Depression: cost-of-illness studies in the international literature, a review. , 2000, The journal of mental health policy and economics.

[60]  L. Mynors-Wallis,et al.  Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care , 2000, BMJ : British Medical Journal.

[61]  H. Anisman,et al.  Treatment of primary dysthymia with group cognitive therapy and pharmacotherapy: clinical symptoms and functional impairments. , 1999, The American journal of psychiatry.

[62]  M. Hautzinger,et al.  Randomised placebo-controlled trial of moclobemide, cognitive–behavioural therapy and their combination in panic disorder with agoraphobia , 1999, British Journal of Psychiatry.

[63]  D. Kupfer,et al.  Treatment of bereavement-related major depressive episodes in later life: a controlled study of acute and continuation treatment with nortriptyline and interpersonal psychotherapy. , 1999, The American journal of psychiatry.

[64]  A. Macaskill,et al.  Rational-emotive therapy plus pharmacotherapy versus pharmacotherapy alone in the treatment of high cognitive dysfunction depression , 1996, Cognitive Therapy and Research.

[65]  K. Power,et al.  Fluvoxamine, placebo, and cognitive behaviour therapy used alone and in combination in the treatment of panic disorder and agoraphobia , 1996 .

[66]  P. Spinhoven,et al.  Panic Management, Trazodone and a Combination of Both in the Treatment of Panic Disorder , 1996 .

[67]  W M Grove,et al.  Cognitive therapy and pharmacotherapy for depression. Singly and in combination. , 1992, Archives of general psychiatry.

[68]  D L Sackett,et al.  An assessment of clinically useful measures of the consequences of treatment. , 1988, The New England journal of medicine.

[69]  M. Hersen,et al.  Social skills training compared with pharmacotherapy and psychotherapy in the treatment of unipolar depression. , 1981, The American journal of psychiatry.

[70]  I. Blackburn,et al.  The Efficacy of Cognitive Therapy in Depression: A Treatment Trial Using Cognitive Therapy and Pharmacotherapy, each Alone and in Combination , 1981, British Journal of Psychiatry.

[71]  G. Klerman,et al.  The efficacy of drugs and psychotherapy in the treatment of acute depressive episodes. , 1979, The American journal of psychiatry.

[72]  J. Higgins,et al.  Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The Cochrane Collaboration , 2013 .

[73]  R. Freire,et al.  Efficacy of a specific model for cognitive-behavioral therapy among panic disorder patients with agoraphobia: a randomized clinical trial. , 2011, Sao Paulo medical journal = Revista paulista de medicina.

[74]  J. Krupnick.  Changes in Self-Schema Structure in Cognitive Therapy for Major Depressive Disorder: A Randomized Clinical Trial , 2011 .

[75]  Alice T. Sawyer,et al.  Is it Beneficial to Add Pharmacotherapy to Cognitive-Behavioral Therapy when Treating Anxiety Disorders? A Meta-Analytic Review. , 2009, International journal of cognitive therapy.

[76]  G. Lewis,et al.  A randomised controlled trial of cognitive behavioural therapy as an adjunct to pharmacotherapy in primary care based patients with treatment resistant depression: a pilot study (ISRCTN81845520) , 2008 .

[77]  Julian P. T. Higgins,et al.  HETEROGI: Stata module to quantify heterogeneity in a meta-analysis , 2005 .

[78]  G. Alexopoulos,et al.  The Treatment Initiation Program: an intervention to improve depression outcomes in older adults. , 2005, The American journal of psychiatry.

[79]  T. Mendelson,et al.  Dialectical behavior therapy for depressed older adults: a randomized pilot study. , 2003, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[80]  S. Batchelder,et al.  Adding group psychotherapy to medication treatment in dysthymia: a randomized prospective pilot study. , 2001, The Journal of psychotherapy practice and research.

[81]  P. Menezes,et al.  A randomized controlled trial comparing moclobemide and moclobemide plus interpersonal psychotherapy in the treatment of dysthymic disorder. , 2001, The Journal of psychotherapy practice and research.

[82]  M. Azhar.  Comparison of Fluvoxamine alone, Fluvoxamine and cognitive psychotherapy and psychotherapy alone in the treatment of panic disorder in Kelantan--implications for management by family doctors. , 2000, The Medical journal of Malaysia.

[83]  M. Hautzinger,et al.  Wirksamkeit Kognitiver Verhaltenstherapie, Pharmakotherapie und deren Kombination bei nicht-endogenen, unipolaren Depressionen. , 1996 .

[84]  A. Dahl,et al.  Does Brief Dynamic Psychotherapy Reduce the Relapse Rate of Panic Disorder? , 1996, European Psychiatry.

[85]  A. Simons,et al.  Cognitive therapy and pharmacotherapy. Singly and together in the treatment of depression. , 1984, Archives of general psychiatry.