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

Cuijpers, Pim; Sijbrandij, Marit; Koole, Sander L.; Andersson, Gerhard; Beekman, Aartjan T.; Reynolds, Charles F.

doi:10.1002/wps.20089

Cited by 424Psychotherapy Techniques and ApplicationsTreatment of Major DepressionAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

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

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Cuijpers, Pim, Sijbrandij, Marit, Koole, Sander L., Andersson, Gerhard, Beekman, Aartjan T., Reynolds, Charles F.·2014·World Psychiatry

DOI 10.1002/wps.20089PMC PMC3918025

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Abstract

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.

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The combination of psychotherapy and pharmacotherapy may be more effective than either alone, but the evidence is not conclusive.
“Other pairwise metaanalyses have found that the combination of psychotherapy and pharmacotherapy may be more effective than either of these alone 11,12 , although the evi dence is not conclusive 13,14 .”
From A network meta‐analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression (2020) · cites this paper as [11]
Existing meta-analyses have compared only two interventions at a time.
“Existing metaanalyses have compared only two in terventions at a time: psychotherapy vs. pharmacotherapy 15 , combined treatment vs. psychotherapy 14 , and combined treat ment vs. pharmacotherapy 11,12 .”
From A network meta‐analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression (2020) · cites this paper as [11]
Earlier meta-analytic work indicated that in depression and anxiety, combining psychotherapy and pharmacotherapy yields an effect equal to adding their separate effects.
“Previous metaanalytic research suggested that the effects of combined treatment in depression and anxiety are the sum of the effects of psychotherapy and those of phar macotherapy 11 .”
From A network meta‐analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression (2020) · cites this paper as [11]
Meta-analyses showed that the combination of medication and psychological therapy was more effective than monotherapy in both current MDD and prevention of relapse/recurrence.
“Meta-analyses indeed showed that the combination of medication and psychological therapy was more effective than monotherapy in both current MDD (Cuijpers et al., 2014;de Maat et al., 2008;Pampallona et al., 2004) and prevention of relapse/ recurrence (Guidi et al., 2011).”
From Adding mindfulness-based cognitive therapy to maintenance antidepressant medication for prevention of relapse/recurrence in major depressive disorder: Randomised controlled trial (2015) · cites this paper as Cuijpers et al., 2014

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Sorted by citations

Depression
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“A combined treatment approach can be useful for patients with MDD. Combined pharmacological and psychological treatments for MDD outperform psychological or pharmacological treatment alone 226,227 for both acute treatment, relapse prevention, and adherence to treatment 181 .”
Anxiety disorders
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“In brief, meta-analytic studies have shown that combination treatment is more effective than pharmacology alone, psychological treatment alone and the combination of psychological treatment and placebo (Cuijpers et al., 2014b; De Maat et al., 2007; Pampallona et al., 2004).”
Background
A network meta‐analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression
Cuijpers, P., Noma, H., Karyotaki, E., Vinkers, C. H., Cipriani, A., & Furukawa, T. A. (2020) · World Psychiatry · doi:10.1002/wps.20701 · Cited by 540 · see citing works
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Craske, M. G., Stein, M. B., Eley, T. C., Milad, M. R., Holmes, A., Rapee, R. M., & Wittchen, H.-U. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.24 · Cited by 652 · see citing works
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“A meta-analysis that looked at studies that examined the use of antidepressants, psychotherapy, and both used in combination found that the use of the combination of antidepressants and psychotherapy offered better treatment outcomes which were still sustained two years later [19].”
Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety
Davis, A. K., Barrett, F. S., & Griffiths, R. R. (2020) · Journal of Contextual Behavioral Science · doi:10.1016/j.jcbs.2019.11.004 · Cited by 375 · see citing works
“Given high prevalence rates and the substantial public health and personal burden of these mental health conditions, numerous interventions have been developed, which include combinations of psychotherapy and pharmacotherapy (Cuijpers et al., 2014; Otto & Hearon, 2016) .”
Background
Technology delivered interventions for depression and anxiety in children and adolescents: a systematic review and meta-analysis
Grist, R., Croker, A., Denne, M., & Stallard, P. (2019) · Clinical Child and Family Psychology Review · doi:10.1007/s10567-018-0271-8 · Cited by 287 · see citing works
Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of panic disorder, social anxiety disorder and generalised anxiety disorder
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“Four studies, including two meta-analyses (Bandelow et al., 2007; Cuijpers et al., 2014a) and two RCTs (Roy-Byrne et al., 2005; Van Apeldoorn et al., 2013) found that the combination of SSRIs and CBT was better than SSRIs alone in the treatment of panic disorder.”
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Sleep and suicide: A systematic review and meta-analysis of longitudinal studies
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Four decades of outcome research on psychotherapies for adult depression: an overview of a series of meta-analyses.
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“…of trials examining these comparisons we found that combined treatment is significantly more effective than pharmacotherapy alone with an effect size of g 0.41 (NNT 4; Cuijpers et al., 2014), and than psychotherapy alone with g 0.35 (NNT 5; Cuijpers, van Straten, Warmerdam, & Andersson, 2009).”
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The experience sampling method as an mHealth tool to support self-monitoring, self-insight, and personalized health care in clinical practice: van Os et al.
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“ioral intervention appears more effective than treatment with medication alone (Cuijpers et al., 2014).”
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More treatment but no less depression: The treatment-prevalence paradox
Ormel, J., Hollon, S. D., Kessler, R. C., Cuijpers, P., & Monroe, S. M. (2022) · Clinical Psychology Review · doi:10.1016/j.cpr.2021.102111 · Cited by 213 · see citing works
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The evidence‐based group‐level symptom‐reduction model as the organizing principle for mental health care: time for change?
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Methodological Recommendations for Trials of Psychological Interventions
Guidi, J., Brakemeier, E.-L., Bockting, C. L. H., Cosci, F., Cuijpers, P., Jarrett, R. B., Linden, M., Marks, I., Peretti, C. S., Rafanelli, C., et al. (2018) · Psychotherapy and Psychosomatics · doi:10.1159/000490574 · Cited by 205 · see citing works
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Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis
Amick, H. R., Gartlehner, G., Gaynes, B. N., Forneris, C., Asher, G. N., Morgan, L. C., Coker-Schwimmer, E., Boland, E., Lux, L. J., Gaylord, S., et al. (2015) · BMJ · doi:10.1136/bmj.h6019 · Cited by 181 · see citing works
Guided self-help works: randomized waitlist controlled trial of pacifica, a mobile app integrating cognitive behavioral therapy and mindfulness for stress, anxiety, and depression
Moberg, C., Niles, A., & Beermann, D. (2019) · Journal of Medical Internet Research · doi:10.2196/12556 · Cited by 157 · see citing works
“Although this finding is inconsistent with some data that combined treatments perform better than therapy alone [61], it is consistent with literature that has found minimal benefit of combining medication with psychotherapy [62].”
Psilocybin-assisted therapy of major depressive disorder using Acceptance and Commitment Therapy as a therapeutic frame
Sloshower, J., Guss, J., Krause, R., Wallace, R. M., Williams, M. T., Reed, S., & Skinta, M. D. (2020) · Journal of Contextual Behavioral Science · doi:10.1016/j.jcbs.2019.11.002 · Cited by 171 · see citing works
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Leyhe, T., Reynolds, C. F., Melcher, T., Linnemann, C., Klöppel, S., Blennow, K., Zetterberg, H., Dubois, B., Lista, S., & Hampel, H. J. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.08.007 · Cited by 168 · see citing works
“[120] Cuijpers P, Sijbrandij M, Sander L, Koole SL, Andersson G, Beekman AT, et al.”
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The Hierarchical Taxonomy of Psychopathology (HiTOP) in psychiatric practice and research
Kotov, R., Cicero, D. C., Conway, C., DeYoung, C. G., Dombrovski, A. Y., Eaton, N. R., First, M. B., Forbes, M. K., Hyman, S. E., Jonas, K. G., et al. (2022) · Psychological Medicine · doi:10.1017/s0033291722001301 · Cited by 163 · see citing works
Machine learning and natural language processing in psychotherapy research: alliance as example use case.
Goldberg, S. B., Flemotomos, N., Martinez, V. R., Tanana, M. J., Kuo, P. B., Pace, B. T., Villatte, J. L., Georgiou, P. G., Van Epps, J., Imel, Z. E., et al. (2020) · Journal of Counseling Psychology · doi:10.1037/cou0000382 · Cited by 141 · see citing works
“Psychotherapy is a frontline treatment approach (Cuijpers et al., 2014), with efficacy similar to psychotropic medications and with potentially longer lasting benefits and fewer side effects (Berwian, Walter, Seifritz, & Huys, 2017).”
Background
A comparison of electronically-delivered and face to face cognitive behavioural therapies in depressive disorders: A systematic review and meta-analysis
Luo, C., Sanger, N., Singhal, N., Pattrick, K., Shams, I., Shahid, H., Hoang, P., Schmidt, J., Lee, J., Haber, S., et al. (2020) · eClinicalMedicine · doi:10.1016/j.eclinm.2020.100442 · Cited by 167 · see citing works
“New research demonstrates that comprehensive treatments include psychotherapy in addition to pharmacotherapy [7,8].”
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5-methoxy-<i>N,N</i>-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety
Davis, A. K., So, S., Lancelotta, R., Barsuglia, J. P., & Griffiths, R. R. (2019) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2018.1545024 · Cited by 142 · see citing works
“interventions have been developed to address these conditions, which include a combination of psychotherapy and pharmacotherapy (9,10).”
Background
Diagnosis and treatment of depression and cognitive impairment in late life
Morimoto, S. S., Kanellopoulos, D., Manning, K. J., & Alexopoulos, G. S. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12669 · Cited by 144 · see citing works
Effectiveness of psychotherapy for treatment-resistant depression: a meta-analysis and meta-regression
van Bronswijk, S., Moopen, N., Beijers, L., Ruhe, H. G., & Peeters, F. (2019) · Psychological Medicine · doi:10.1017/s003329171800199x · Cited by 128 · see citing works
“However, a recent meta-analysis on combination therapy (pharmacotherapy and psychotherapy) for depression and anxiety disorders has shown equal and independent effects of pharmacotherapy and psychotherapy (Cuijpers et al., 2014).”
BackgroundMethod
A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive–compulsive disorder in children/adolescents and adults
Skapinakis, P., Caldwell, D. M., Hollingworth, W., Bryden, P. A., Fineberg, N. A., Salkovskis, P. M., Welton, N. J., Baxter, H., Kessler, D. S., Churchill, R. C., et al. (2016) · Health Technology Assessment · doi:10.3310/hta20430 · Cited by 133 · see citing works
Improving the Efficiency of Psychotherapy for Depression: Computer-Assisted Versus Standard CBT
Thase, M. E., Wright, J. H., Eells, T. D., Barrett, M. S., Wisniewski, S. R., Balasubramani, G. K., McCrone, P., & Brown, G. K. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17010089 · Cited by 131 · see citing works
Psychological treatment of depression: A systematic overview of a 'Meta-Analytic Research Domain'
Cuijpers, P., Miguel, C., Harrer, M., Plessen, C. Y., Ciharova, M., Papola, D., Ebert, D., & Karyotaki, E. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.05.011 · Cited by 136 · see citing works
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Bereavement: Course, Consequences, and Care
Zisook, S., Iglewicz, A., Avanzino, J. A., Maglione, J. E., Glorioso, D., Zetumer, S. D., Seay, K., Vahia, I. V., Young, I. T., Lebowitz, B. D., et al. (2014) · Current Psychiatry Reports · doi:10.1007/s11920-014-0482-8 · Cited by 132 · see citing works
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Naturalistic Use of Mescaline Is Associated with Self-Reported Psychiatric Improvements and Enduring Positive Life Changes
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Standardization of health outcomes assessment for depression and anxiety: recommendations from the ICHOM Depression and Anxiety Working Group
Obbarius, A., van Maasakkers, L., Baer, L., Clark, D. M., Crocker, A. G., de Beurs, E., Emmelkamp, P. M. G., Furukawa, T. A., Hedman-Lagerlöf, E., Kangas, M., et al. (2017) · Quality of Life Research · doi:10.1007/s11136-017-1659-5 · Cited by 116 · see citing works
“A variety of treatment options have been proven effective in reducing symptom burden and improving functioning for patients with depression or anxiety [4].”
Background
Honey, I shrunk the pooled SMD! Guide to critical appraisal of systematic reviews and meta-analyses using the Cochrane review on exercise for depression as example
Ekkekakis, P. (2015) · Mental Health and Physical Activity · doi:10.1016/j.mhpa.2014.12.001 · Cited by 114 · see citing works
Unconscious emotion: A cognitive neuroscientific perspective
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Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Sehatzadeh, S., Tu, H., Palimaka, S., Yap, B., O’Reilly, D. J., & Bowen, J. M. (2016) · Cited by 102 · see citing works
Management of depressive symptoms in peri- and postmenopausal women: EMAS position statement
Stute, P., Spyropoulou, A. C., Karageorgiou, V., Cano, A., Bitzer, J., Ceauşu, I., Chedraui, P. A., Durmuşoğlu, F., Erkkola, R. U., Goulis, D. G., et al. (2019) · Maturitas · doi:10.1016/j.maturitas.2019.11.002 · Cited by 102 · see citing works
“The preference expressed by patients for psychological interventions, their efficacy (in particular in combination with antidepressants) and their comparative safety suggest that the combination of treatment methods might be the optimal strategy for managing major depressive disorder [85].”
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PTSD Treatment for Veterans: What's Working, What's New, and What's Next.
Reisman, M. (2016) · PubMed Central · Cited by 97 · see citing works
Antidepressants in inflammatory bowel disease
Mikocka-Walus, A., Ford, A. C., & Drossman, D. A. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0259-y · Cited by 93 · see citing works
Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments
Greenway, K. T., Garel, N., Jerome, L., & Feduccia, A. A. (2020) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2020.1772054 · Cited by 94 · see citing works
“Combining antidepressants with psychotherapy to treat depression is often framed in terms of additive benefits via distinct mechanisms, and indeed response rates are typically greater than either in isolation [24], especially in terms of”
Background
The effects of cognitive behavioral and mindfulness-based therapies on psychological distress in patients with multiple sclerosis, Parkinson's disease and Huntington's disease: Two meta-analyses
Ghielen, I., Rutten, S., Boeschoten, R. E., Houniet-de Gier, M., van Wegen, E. E. H., van den Heuvel, O. A., & Cuijpers, P. (2019) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2019.05.001 · Cited by 74 · see citing works
“It is also argued that a combination of psychotherapy and pharmacotherapy might be most beneficial, at least for outpatients with chronic forms of depression [52,53] and panic disorder [53].”
BackgroundSelf-citation
Trends in Outpatient Psychotherapy Provision by U.S. Psychiatrists: 1996–2016
Tadmon, D., & Olfson, M. (2021) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2021.21040338 · Cited by 70 · see citing works
Long-Term Pharmacological Treatments of Anxiety Disorders: An Updated Systematic Review
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Benefits of Sequentially Adding Cognitive-Behavioral Therapy or Antidepressant Medication for Adults With Nonremitting Depression
Dunlop, B. W., LoParo, D., Kinkead, B. L., Mletzko, T., Cole, S. P., Nemeroff, C. B., Mayberg, H. S., & Craighead, W. E. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.18091075 · Cited by 65 · see citing works
“and psychotherapy on depression are largely independent (59).”
Psychotherapies for adult depression: recent developments
Cuijpers, P. (2015) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000121 · Cited by 64 · see citing works
Self-citation
Neural mechanisms of emotion regulation and their role in endocrine and immune functioning: A review with implications for treatment of affective disorders
Lopez, R. B., Denny, B. T., & Fagundes, C. P. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.10.019 · Cited by 64 · see citing works
“medication alone), and even then effect sizes remain modest (i.e., Hedge’s g=0.41 for depressive disorders, 0.47 for anxiety disorders; Cuijpers et al., 2014).”
Influential
Depression in primary care: part 2—management
Ramanuj, P., Ferenchick, E. K., & Pincus, H. A. (2019) · BMJ · doi:10.1136/bmj.l835 · Cited by 62 · see citing works
Toward Synergies of Ketamine and Psychotherapy
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Depression and psychodynamic psychotherapy
Ribeiro, Â. D. S. B., Ribeiro, J. P., & von Doellinger, O. (2017) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2016-2107 · Cited by 61 · see citing works
Dopamine dysregulation hypothesis: the common basis for motivational anhedonia in major depressive disorder and schizophrenia?
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Discontinuation of antidepressant medication after mindfulness-based cognitive therapy for recurrent depression: randomised controlled non-inferiority trial
Huijbers, M. J., Spinhoven, P., Spijker, J., Ruhé, H. G., van Schaik, D. J. F., van Oppen, P., Nolen, W. A., Ormel, J., Kuyken, W., van der Wilt, G. J., et al. (2016) · British Journal of Psychiatry · doi:10.1192/bjp.bp.115.168971 · Cited by 58 · see citing works
“Our results seem to be in line with evidence that combination therapy is more effective than monotherapy in the acute treatment of major depressive disorder 33 and also for prevention of relapse/ recurrence.”
The medical model and its application in mental health
Huda, A. S. (2020) · International Review of Psychiatry · doi:10.1080/09540261.2020.1845125 · Cited by 58 · see citing works
“In depression and anxiety for example, a combination of antidepressants and psychotherapy is more effective than just antidepressants (Cuijpers et al., 2014).”
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Efficacy and cost-effectiveness of guided and unguided internet- and mobile-based indicated transdiagnostic prevention of depression and anxiety (ICare Prevent): a three-armed randomized controlled trial in four European countries.
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DEPRESSION AND ANXIETY 26:279–288 (2009) Research Article PSYCHOTHERAPY VERSUS THE COMBINATION OF PSYCHOTHERAPY AND PHARMACOTHERAPY IN THE TREATMENT OF DEPRESSION: A META-ANALYSIS
Cuijpers, P. J., Ph., D., van Straten, A., Ph., D., Warmerdam, L., Andersson, G., & Ph., D. (2016)
Self-citation

Authors: Cuijpers, P., Sijbrandij, M., Koole, S. L., Andersson, G., Beekman, A. T., & Reynolds, C. F.
Affiliations: Leuphana University of Lüneburg (DE)
Amsterdam Public Health (NL)
Linköping University (SE)
University of Pittsburgh (US)
ORCID: Cuijpers, Pim
Sijbrandij, Marit
Koole, Sander L.
Andersson, Gerhard
Beekman, Aartjan T.
Reynolds, Charles F.
Venue: World Psychiatry
Publisher: Wiley
Published: 2014-02
Volume: 13
Issue: 1
Pages: 56-67
ISSN: 1723-8617 (ISSN-L)
DOI: 10.1002/wps.20089
PMC: PMC3918025
OpenAlex: W2053011811
Cited by: 424
References: 87
Citations by year: 2026: 17 · 2025: 25 · 2024: 24 · 2023: 45 · 2022: 34 · 2021: 72 · 2020: 36 · 2019: 37 · 2018: 36 · 2017: 29 · 2016: 37 · 2015: 20 · 2014: 11 · 2012: 1
FWCI: 4.89
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 577 d)
Locations: World Psychiatry (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion, other-oa)
VU Research Portal (submittedVersion, other-oa)
Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
Pure Amsterdam UMC (submittedVersion, other-oa)
Multilingual Matters (Channel View Publications) (submittedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders: National Institutes of Health (UL1TR000005)
National Institute of Mental Health (P30MH090333)
National Center for Advancing Translational Sciences
Topics: Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords: combined psychotherapy and pharmacotherapy, antidepressants, depression, anxiety disorders, major depressive disorder, panic disorder, obsessive-compulsive disorder, treatment effect comparison, number needed to treat, long-term treatment outcomes

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

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