Antidepressants for treatment of depression in primary care: a systematic review and meta-analysis
Bruce Arroll 1 , Weng-yee Chin 2 , Waldron Martis 1 , Felicity Goodyear-Smith 1 , Vicki Mount 3 , Douglas Kingsford 4 , Stephen Humm 5 , Grant Blashki 6 , Stephen MacGillivray 71 Department of General Practice and Primary Health Care, University of Auckland, Auckland, New Zealand
2 Department of Family Medicine & Primary Care and Institute of Medical and Health Sciences Education, University of Hong Kong, Hong Kong
3 Auckland City Hospital, Grafton, Auckland, New Zealand
4 Chief Medical Information Officer & Executive Medical Director Interior Health Authority, Kelowna, British Columbia, Canada
5 Christchurch PsychMed, Christchurch, New Zealand
6 Department of General Practice, University of Melbourne, Melbourne, Australia
7 Evidence Synthesis Training and Research Group, Centre for Health and Related Research, University of Dundee, Dundee, Scotland
Correspondence to: Bruce Arroll, Department of General Practice and Primary Health Care, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Email: bruce.arroll@auckland.ac.nz
Journal of Primary Health Care 8(4) 325-334 https://doi.org/10.1071/HC16008
Published: 21 December 2016
Journal Compilation © Royal New Zealand College of General Practitioners 2016.
This is an open access article licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Abstract
INTRODUCTION: Evidence for the effectiveness of drug treatment for depression in primary care settings remains limited, with little information on newer antidepressant classes.
AIM: To update an earlier Cochrane review on the effectiveness of antidepressants in primary care to include newer antidepressant classes, and to examine the efficacy of individual agents.
METHODS: Selection criteria included antidepressant studies with a randomly assigned placebo group where half or more subjects were recruited from primary care. The Cochrane Collaboration Depression, Anxiety and Neurosis (CCDAN) group searched multiple databases to identify eligible studies. Data extraction was performed independently by two reviewers. Data were analysed using Revman version 5.3.5.
RESULTS: In total, 17 papers and 22 comparisons were included for analysis. Significant benefits in terms of response were found for tricyclic antidepressants (TCA) with a relative risk (RR) = 1.23 (95% CI, 1.01–1.48), and serotonin selective reuptake inhibitors (SSRI) with a RR = 1.33 (95% CI, 1.20–1.48). Mianserin was effective for continuous outcomes. Numbers needed to treat (NNT) for TCA = 8.5; SSRI = 6.5; and venlafaxine = 6. Most studies were industry-funded and of a brief duration (≤ 8 weeks). There was evidence of publication bias. There were no studies comparing newer antidepressants against placebo.
CONCLUSION: Antidepressants such as TCA, SSRI, SNRI (serotonin–norepinephrine reuptake inhibitor) and NaSSA (noradrenergic and specific serotonergic antidepressant) classes appear to be effective in primary care when compared with placebo. However, in view of the potential for publication bias and that only four studies were not funded by industry, caution is needed when considering their use in primary care.
KEYWORDS: Antidepressant agents; primary health care; placebos; clinical trial; meta-analysis; general practice
References
[1] Gilbody S, Gask L. Depressive disorders in primary care: a review. In: Herrman H, Maj M, Sartorius N, eds. Depressive Disorders. Hoboken, NJ: John Wiley & Sons, Ltd; 2009. p. 271–318.[2] Mitchell AJ, Vaze A, Rao S. Clinical diagnosis of depression in primary care: a meta-analysis. Lancet. 2009; 374 609–19.
| Clinical diagnosis of depression in primary care: a meta-analysis.Crossref | GoogleScholarGoogle Scholar |
[3] Schwenk TL, Coyne JC, Fechner-Bates S. Differences between detected and undetected patients in primary care and depressed psychiatric patients. Gen Hosp Psychiatry. 1996; 18 407–15.
| Differences between detected and undetected patients in primary care and depressed psychiatric patients.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2s%2Fpt1answ%3D%3D&md5=3feb04a51f2945f752eb3b027ff17e12CAS |
[4] Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008; 5 e45
| Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration.Crossref | GoogleScholarGoogle Scholar |
[5] Ioannidis JP. Why most published research findings are false. PLoS Med. 2005; 2 e124
| Why most published research findings are false.Crossref | GoogleScholarGoogle Scholar |
[6] Arroll B, Elley CR, Fishman T, et al. Antidepressants versus placebo for depression in primary care. Cochrane Database Syst Rev. 2009; 2009 CD007954
[7] Cipriani A, Furukawa T, Salanti G, et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 2009; 373 746–58.
| Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXisVOrtr8%3D&md5=300eefb7554eb35794db4198bb2de18cCAS |
[8] Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009; 339 b2535
| Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.Crossref | GoogleScholarGoogle Scholar |
[9] Lepola U, Loft H, Reines EH. Escitalopram is efficacious and well tolerated for the treatment of depression in primary care. Annual Meeting of the American Medical Association, New Orleans. 2001.
[10] Montgomery SA, Loft H, Sanchez C, Reines EH, Papp M. Escitalopram (s enantiomer of Citalopram): clinical efficacy and onset of action predicted from a rat model. Pharmacol Toxicol. 2001; 88 282–6.
| Escitalopram (s enantiomer of Citalopram): clinical efficacy and onset of action predicted from a rat model.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXktVWmtbc%3D&md5=6c522abf955cf59b9fc749a0fdaf38a9CAS |
[11] Lepola UM, Loft H, Reines EH. Escitalopram (10–20 mg/day) is effective and well tolerated in a placebo controlled study in depression in primary care. Int Clin Psychopharmacol. 2003; 18 211–7.
| Escitalopram (10–20 mg/day) is effective and well tolerated in a placebo controlled study in depression in primary care.Crossref | GoogleScholarGoogle Scholar |
[12] Feighner JP. Mechanism of action of antidepressant medications. J Clin Psychiatry. 1999; 60(Suppl 4) 4–11.
[13] Linde K, Kriston L, Rucker G, et al. Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis. Ann Fam Med. 2015; 13 69–79.
| Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis.Crossref | GoogleScholarGoogle Scholar |
[14] Bjerkenstedt L, Edman GV, Alken RG, Mannel M. Hypericum extract LI 160 and fluoxetine in mild to moderate depression. A randomized, placebo-controlled multi-center study in outpatients. Eur Arch Psychiatry Clin Neurosci. 2005; 255 40–7.
| Hypericum extract LI 160 and fluoxetine in mild to moderate depression. A randomized, placebo-controlled multi-center study in outpatients.Crossref | GoogleScholarGoogle Scholar |
[15] Gastpar M, Singer A, Zeller K. Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double- blind, randomised, multicentre, placebo-controlled study. Pharmacopsychiatry. 2006; 39 66–75.
| Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double- blind, randomised, multicentre, placebo-controlled study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjvFOgtbc%3D&md5=7ce275ab1cca305d7559c2a87669ceeaCAS |
[16] Lecrubier Y, Bourin M, Moon CA, et al. Efficacy of venlafaxine in depressive illness. Acta Psychiatr Scand. 1997; 95 485–93.
| Efficacy of venlafaxine in depressive illness.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXkvVGjsLg%3D&md5=b8e610827bc99d9ae29c26a4abee3b34CAS |
[17] American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th edition) DSM-IV-TR. Washington, DC: APA; 2000.
[18] Hegerl U, Hautzinger M, Mergl R, et al. Effects of pharmacotherapy and psychotherapy in depressed primary-care patients: a randomized, controlled trial including a patients’ choice arm. Int J Neuropsychopharmacol. 2010; 13 31–44.
| Effects of pharmacotherapy and psychotherapy in depressed primary-care patients: a randomized, controlled trial including a patients’ choice arm.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXovVartw%3D%3D&md5=d2a33662ae5b36161c38bb56ebe5f180CAS |
[19] Miller SM, Naylor GJ, Murtagh M, Winslow G. A double-blind comparison of paroxetine and placebo in the treatment of depressed patients in a psychiatric outpatient clinic. Acta Psychiatr Scand. 1989; 80(Suppl 350) 143–4.
| A double-blind comparison of paroxetine and placebo in the treatment of depressed patients in a psychiatric outpatient clinic.Crossref | GoogleScholarGoogle Scholar |
[20] Thompson C, Thompson CM. The prescribing of antidepressants in general practice. II A placebo controlled trial of low-dose dothiepin. Hum Psychopharmacol. 1989; 4 191–204.
| The prescribing of antidepressants in general practice. II A placebo controlled trial of low-dose dothiepin.Crossref | GoogleScholarGoogle Scholar |
[21] Thomson J, Rankin H, Ashcroft GW, Yates CM, McQueen JK, Cummings SW. The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline and a combination of L-tryptophan and amitriptyline with placebo. Pscyhol Med. 1982; 12 741–51.
| The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline and a combination of L-tryptophan and amitriptyline with placebo.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL3s7hvVWltA%3D%3D&md5=a642aec278e2db6db360832ce2b5dfabCAS |
[22] Undurraga J, Baldessarini RJ. Randomized, placebo-controlled trials of antidepressants for acute major depression: thirty-year meta-analytic review. Neuropsychopharmacology. 2012; 37 851–64.
| Randomized, placebo-controlled trials of antidepressants for acute major depression: thirty-year meta-analytic review.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XitlKitbg%3D&md5=91b5535de7087d0a1845bc878d0ab2acCAS |
[23] Wiles NJ, Mulligan J, Peters TJ, et al. Severity of depression and response to antidepressants: GENPOD randomised controlled trial. Br J Psychiatry. 2012; 200 130–6.
| Severity of depression and response to antidepressants: GENPOD randomised controlled trial.Crossref | GoogleScholarGoogle Scholar |
[24] Cameron IM, Reid IC, MacGillivray SA. Efficacy and tolerability of antidepressants for sub-threshold depression and for mild major depressive disorder. J Affect Disord. 2014; 166 48–58.
| Efficacy and tolerability of antidepressants for sub-threshold depression and for mild major depressive disorder.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtFWnu7jI&md5=fafb27fd05760bd99e63f35ee7061badCAS |
[25] Barge-Schaapveld DQCM, Nicholson NA. Effects of antidepressant treatment on the quality of daily life: an experience sampling study. J Clin Psychiatry. 2002; 63 477–85.
| Effects of antidepressant treatment on the quality of daily life: an experience sampling study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XlsFSrsrg%3D&md5=26cfbd50be903665412dbdc8675671eaCAS |
[26] Blashki TG, Mowbray R, Davies B. Controlled trials of amitriptyline in general practice. BMJ. 1971; 1 133–8.
| Controlled trials of amitriptyline in general practice.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE3M%2FnvFGluw%3D%3D&md5=f0920cd3ad3e113a7a5fdf3a6f81c482CAS |
[27] Doogan DP, Langdon CJ. A double-blind, placebo controlled comparison of sertraline and dothiepin in the treatment of major depression in general practice. Int Clin Psychopharmacol. 1994; 9 95–100.
| A double-blind, placebo controlled comparison of sertraline and dothiepin in the treatment of major depression in general practice.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2czjsVGmug%3D%3D&md5=f75841fb866b175edf83085e1aba7976CAS |
[28] Hollyman JA, Freeling P, Paykell ES, Bhat A, Sedgwick P. Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice. J R Coll Gen Pract. 1988; 38 393–7.
| 1:STN:280:DyaL1Mzot1CgsQ%3D%3D&md5=1fb19ef046d0fa6e3aa433fc2c9f6427CAS |
[29] Mynors-Wallis LM, Gath DH, Lloyd-thomas AR, Tomlinson D. Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care. BMJ. 1995; 310 441–5.
| Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2M7nvV2huw%3D%3D&md5=5e715dbd793a8e85a2bd387ffe183573CAS |
[30] Philipp M, Kohnen R, Hiller KO. Hypercium extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. BMJ. 1999; 319 1534–8.
| Hypercium extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3c%2FlvFCmtg%3D%3D&md5=dc373d0c0d72c1c4853fdcb8a01fb6e0CAS |
[31] Malt UF, Robak OH, Madsbu H-P, Bakke O, Loeb M. The Norwegian naturalistic treatment study of depression in general practice (NORDEP)-1: randomised double blind study. BMJ. 1999; 318 1180–4.
| The Norwegian naturalistic treatment study of depression in general practice (NORDEP)-1: randomised double blind study.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1M3jvVKmsQ%3D%3D&md5=b9597db8936d8e509ad7ce63c6022dd6CAS |
[32] Wade A, Lemming OM, Hedegaard KB. Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol. 2002; 17 95–102.
| Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD383ktlantg%3D%3D&md5=4d907631837816bb59d33472d9baffceCAS |
[33] Brink CW, vd Krogt JP, Dunbar GC, Behagel LH. A controlled clinical trial of mianserin and placebo in the treatment of depression in general practice. J Drug Ther Res. 1984; 9 513–7.
