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Meta-Analysis
. 2003;2003(3):CD003197.
doi: 10.1002/14651858.CD003197.

Low dosage tricyclic antidepressants for depression

T Furukawa  1 , H McGuire, C Barbui
Affiliations
Meta-Analysis

Low dosage tricyclic antidepressants for depression

T Furukawa et al. Cochrane Database Syst Rev. 2003.

Abstract

Background: Tricyclic antidepressants are still extensively prescribed worldwide. Evidence for the recommended dosage of tricyclics, however, is poor.

Objectives: To compare the effects and side effects of low dosage tricyclic antidepressants with placebo and with standard dosage tricyclics in acute phase treatment of depression.

Search strategy: Electronic search of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), incorporating results of group searches of MEDLINE (1966-), EMBASE (1980-), CINAHL (1982-), PsycLIT (1974-), PSYNDEX (1977-) and LILACS (1982-1999) and hand searches of major psychiatric and medical journals. Reference search and SciSearch of the identified studies. Personal contact with authors of significant papers.

Selection criteria: All randomised controlled trials 1) comparing low dosage TCA (=< 100 mg/d on average at the end of trial) with placebo or 2) comparing low and standard dosages of the same TCA, in acute phase treatment of depressive disorder

Data collection and analysis: Two independent reviewers examined eligibility of the identified studies, and extracted data for outcomes at 1 week, 2 weeks, 4 weeks, 6-8 weeks and later. Main outcome measures were relative risk of response in depression (random effects model), according to the original authors' definition but usually defined as 50% or greater reduction in severity of depression according to the last-observation-carried-forward intention-to-treat method, and relative risks of overall dropouts and dropouts due to side effects. Other outcome measures included worst-case-scenario intention-to-treat analysis of response as defined above (in which dropouts were considered non-responders in the active treatment group and as responders in the comparison group), and standardised weighted mean scores of continuous depression severity scales (usually calculated by last-observation-carried-forward method).

Main results: 35 studies (2013 participants) compared low dosage tricyclics with placebo, and six studies (551 participants) compared low dosage tricyclics with standard dosage tricyclics. Low dosage tricyclics, mostly between 75 and 100 mg/day, were 1.65 (95% confidence interval 1.36 to 2.0) and 1.47 (1.12 to 1.94) times more likely than placebo to bring about response at 4 weeks and 6-8 weeks, respectively. Standard dosage tricyclics failed, however, to bring about more response but produced more dropouts due to side effects than low dosage tricyclics.

Reviewer's conclusions: Treatment of depression in adults with low dose tricyclics is justified. However, more rigorous studies are needed to definitively establish the relative benefits and harms of varying dosages.

PubMed Disclaimer

Conflict of interest statement

TAF has received fees for speaking from several pharmaceutical companies, some of which manufacture various types of antidepressants such as trazodone, paroxetine, fluvoxamine and milnacipran.

Figures

1.1
1.1. Analysis
Comparison 1 ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 1 Acceptability of treatment as measured by leaving study early for any reason.
1.2
1.2. Analysis
Comparison 1 ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 2 Depression severity.
1.3
1.3. Analysis
Comparison 1 ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 3 Depression improved (per protocol).
1.4
1.4. Analysis
Comparison 1 ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 4 Depression improved (worst case ITT).
1.5
1.5. Analysis
Comparison 1 ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 5 Side effects 1. Drop‐outs due to side effects.
1.6
1.6. Analysis
Comparison 1 ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 6 Side effects 2. Total number experiencing at least one side effect.
1.7
1.7. Analysis
Comparison 1 ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 7 Depression improved (per protocol) for funnel plot analysis.
2.1
2.1. Analysis
Comparison 2 ANY DEPRESSION: Low dosage TCA vs Placebo (excluding Brick, Rampello, Jacobson, Hollanda, Nandi, Tetreault), Outcome 1 Acceptability of treatment as measured by leaving study early for any reason.
2.2
2.2. Analysis
Comparison 2 ANY DEPRESSION: Low dosage TCA vs Placebo (excluding Brick, Rampello, Jacobson, Hollanda, Nandi, Tetreault), Outcome 2 Depression severity.
2.3
2.3. Analysis
Comparison 2 ANY DEPRESSION: Low dosage TCA vs Placebo (excluding Brick, Rampello, Jacobson, Hollanda, Nandi, Tetreault), Outcome 3 Depression improved (per protocol).
2.4
2.4. Analysis
Comparison 2 ANY DEPRESSION: Low dosage TCA vs Placebo (excluding Brick, Rampello, Jacobson, Hollanda, Nandi, Tetreault), Outcome 4 Depression improved (worst case ITT).
2.5
2.5. Analysis
Comparison 2 ANY DEPRESSION: Low dosage TCA vs Placebo (excluding Brick, Rampello, Jacobson, Hollanda, Nandi, Tetreault), Outcome 5 Side effects 1. Drop‐outs due to side effects.
2.6
2.6. Analysis
Comparison 2 ANY DEPRESSION: Low dosage TCA vs Placebo (excluding Brick, Rampello, Jacobson, Hollanda, Nandi, Tetreault), Outcome 6 Side effects 2. Total number experiencing at least one side effect.
3.1
3.1. Analysis
Comparison 3 OPERATIONALLY DEFINED DEPRESSION: Low dosage TCA vs Placebo, Outcome 1 Acceptability of treatment as measured by leaving study early for any reason.
3.2
3.2. Analysis
Comparison 3 OPERATIONALLY DEFINED DEPRESSION: Low dosage TCA vs Placebo, Outcome 2 Depression severity.
3.3
3.3. Analysis
Comparison 3 OPERATIONALLY DEFINED DEPRESSION: Low dosage TCA vs Placebo, Outcome 3 Depression improved (per protocol).
3.4
3.4. Analysis
Comparison 3 OPERATIONALLY DEFINED DEPRESSION: Low dosage TCA vs Placebo, Outcome 4 Depression improved (worst case ITT).
3.5
3.5. Analysis
Comparison 3 OPERATIONALLY DEFINED DEPRESSION: Low dosage TCA vs Placebo, Outcome 5 Side effects 1. Drop‐outs due to side effects.
3.6
3.6. Analysis
Comparison 3 OPERATIONALLY DEFINED DEPRESSION: Low dosage TCA vs Placebo, Outcome 6 Side effects 2. Total number experiencing at least one side effect.
4.1
4.1. Analysis
Comparison 4 ANY DEPRESSION: Strictly low dosage TCA vs Placebo, Outcome 1 Acceptability of treatment as measured by leaving study early for any reason.
4.2
4.2. Analysis
Comparison 4 ANY DEPRESSION: Strictly low dosage TCA vs Placebo, Outcome 2 Depression severity.
4.3
4.3. Analysis
Comparison 4 ANY DEPRESSION: Strictly low dosage TCA vs Placebo, Outcome 3 Depression improved (per protocol).
4.4
4.4. Analysis
Comparison 4 ANY DEPRESSION: Strictly low dosage TCA vs Placebo, Outcome 4 Depression improved (worst case ITT).
4.5
4.5. Analysis
Comparison 4 ANY DEPRESSION: Strictly low dosage TCA vs Placebo, Outcome 5 Side effects 1. Drop‐outs due to side effects.
4.6
4.6. Analysis
Comparison 4 ANY DEPRESSION: Strictly low dosage TCA vs Placebo, Outcome 6 Side effects 2. Total number experiencing at least one side effect.
5.1
5.1. Analysis
Comparison 5 OLD PEOPLE WITH ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 1 Acceptability of treatment as measured by leaving study early for any reason.
5.2
5.2. Analysis
Comparison 5 OLD PEOPLE WITH ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 2 Depression severity.
5.3
5.3. Analysis
Comparison 5 OLD PEOPLE WITH ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 3 Depression improved (per protocol).
5.4
5.4. Analysis
Comparison 5 OLD PEOPLE WITH ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 4 Depression improved (worst case ITT).
5.5
5.5. Analysis
Comparison 5 OLD PEOPLE WITH ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 5 Side effects 1. Drop‐outs due to side effects.
5.6
5.6. Analysis
Comparison 5 OLD PEOPLE WITH ANY DEPRESSION: Low dosage TCA vs Placebo, Outcome 6 Side effects 2. Total number experiencing at least one side effect.
6.1
6.1. Analysis
Comparison 6 ANY DEPRESSION IN PRIMARY CARE: Low dosage TCA vs Placebo, Outcome 1 Acceptability of treatment as measured by leaving study early for any reason.
6.2
6.2. Analysis
Comparison 6 ANY DEPRESSION IN PRIMARY CARE: Low dosage TCA vs Placebo, Outcome 2 Depression severity.
6.3
6.3. Analysis
Comparison 6 ANY DEPRESSION IN PRIMARY CARE: Low dosage TCA vs Placebo, Outcome 3 Depression improved (per protocol).
6.4
6.4. Analysis
Comparison 6 ANY DEPRESSION IN PRIMARY CARE: Low dosage TCA vs Placebo, Outcome 4 Depression improved (worst case ITT).
6.5
6.5. Analysis
Comparison 6 ANY DEPRESSION IN PRIMARY CARE: Low dosage TCA vs Placebo, Outcome 5 Side effects 1. Drop‐outs due to side effects.
6.6
6.6. Analysis
Comparison 6 ANY DEPRESSION IN PRIMARY CARE: Low dosage TCA vs Placebo, Outcome 6 Side effects 2. Total number experiencing at least one side effect.
7.1
7.1. Analysis
Comparison 7 ANY DEPRESSION AMONG PSYCHIATRIC PATIENTS: Low dosage TCA vs Placebo, Outcome 1 Acceptability of treatment as measured by leaving study early for any reason.
7.2
7.2. Analysis
Comparison 7 ANY DEPRESSION AMONG PSYCHIATRIC PATIENTS: Low dosage TCA vs Placebo, Outcome 2 Depression severity.
7.3
7.3. Analysis
Comparison 7 ANY DEPRESSION AMONG PSYCHIATRIC PATIENTS: Low dosage TCA vs Placebo, Outcome 3 Depression improved (per protocol).
7.4
7.4. Analysis
Comparison 7 ANY DEPRESSION AMONG PSYCHIATRIC PATIENTS: Low dosage TCA vs Placebo, Outcome 4 Depression improved (worst case ITT).
7.5
7.5. Analysis
Comparison 7 ANY DEPRESSION AMONG PSYCHIATRIC PATIENTS: Low dosage TCA vs Placebo, Outcome 5 Side effects 1. Drop‐outs due to side effects.
7.6
7.6. Analysis
Comparison 7 ANY DEPRESSION AMONG PSYCHIATRIC PATIENTS: Low dosage TCA vs Placebo, Outcome 6 Side effects 2. Total number experiencing at least one side effect.
8.1
8.1. Analysis
Comparison 8 ANY DEPRESSION: Very low dosage TCA vs Placebo, Outcome 1 Acceptability of treatment as measured by leaving study early for any reason.
8.2
8.2. Analysis
Comparison 8 ANY DEPRESSION: Very low dosage TCA vs Placebo, Outcome 2 Depression severity.
8.3
8.3. Analysis
Comparison 8 ANY DEPRESSION: Very low dosage TCA vs Placebo, Outcome 3 Depression improved (per protocol).
8.4
8.4. Analysis
Comparison 8 ANY DEPRESSION: Very low dosage TCA vs Placebo, Outcome 4 Depression improved (worst case ITT).
8.5
8.5. Analysis
Comparison 8 ANY DEPRESSION: Very low dosage TCA vs Placebo, Outcome 5 Side effects 1. Drop‐outs due to side effects.
8.6
8.6. Analysis
Comparison 8 ANY DEPRESSION: Very low dosage TCA vs Placebo, Outcome 6 Side effects 2. Total number experiencing at least one side effect.
9.1
9.1. Analysis
Comparison 9 Low dosage TCA vs Standard dosage TCA, Outcome 1 Acceptability of treatment as measured by leaving study early for any reason.
9.2
9.2. Analysis
Comparison 9 Low dosage TCA vs Standard dosage TCA, Outcome 2 Depression severity.
9.3
9.3. Analysis
Comparison 9 Low dosage TCA vs Standard dosage TCA, Outcome 3 Depression improved (per protocol).
9.4
9.4. Analysis
Comparison 9 Low dosage TCA vs Standard dosage TCA, Outcome 4 Depression improved (worst case ITT).
9.5
9.5. Analysis
Comparison 9 Low dosage TCA vs Standard dosage TCA, Outcome 5 Side effects 1. Drop‐outs due to side effects.
9.6
9.6. Analysis
Comparison 9 Low dosage TCA vs Standard dosage TCA, Outcome 6 Side effects 2. Total number experiencing at least one side effect.
See this image and copyright information in PMC

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