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Meta-Analysis
. 2011 Dec 7;2011(12):CD002950.
doi: 10.1002/14651858.CD002950.pub3.

Antidepressants for cocaine dependence and problematic cocaine use

Pier Paolo Pani  1 , Emanuela Trogu, Simona Vecchi, Laura Amato
Affiliations
Meta-Analysis

Antidepressants for cocaine dependence and problematic cocaine use

Pier Paolo Pani et al. Cochrane Database Syst Rev. .

Abstract

Background: Cocaine dependence is a disorder for which no pharmacological treatment of proven efficacy exists, advances in the neurobiology could guide future medication development.

Objectives: To investigate the efficacy and acceptability of antidepressants alone or in combination with any psychosocial intervention for the treatment of cocaine dependence and problematic cocaine use.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE and CINAHL in July 2011 and researchers for unpublished trials.

Selection criteria: Randomised clinical trials comparing antidepressants alone or associated with psychosocial intervention with placebo, no treatment, other pharmacological or psychosocial interventions.

Data collection and analysis: Two authors independently assessed trial quality and extracted data.

Main results: 37 studies were included in the review (3551 participants).Antidepressants versus placebo: results for dropouts did not show evidence of difference, 31 studies, 2819 participants, RR 1.03 (Cl 95% 0.93 to 1.14). Looking at Abstinence from cocaine use, even though not statistically significant, the difference shown by the analysis in the three-weeks abstinence rate was in favour of antidepressants (eight studies, 942 participants, RR 1.22 (Cl 95% 0.99 to 1.51)). Considering only studies involving tricyclics, five studies, 367 participants, or only desipramine, four studies, 254 participants, the evidence was in favour of antidepressants. However, selecting only studies with operationally defined diagnostic criteria, statistical significance favouring antidepressants, as well as the trend for significance shown by the full sample, disappeared. Looking at safety issues, the results did not show evidence of differences (number of patients withdrawn for medical reasons, thirteen studies, 1396 participants, RR 1.39 (Cl 95% 0.91 to 2.12)). Subgroup analysis considering length of the trial, associated opioid dependence or associated psychosocial interventions as confounding factors, failed in showing consistent and statistically significant differences in favour of antidepressants.Antidepressants versus other drugs: Comparing antidepressants with dopamine agonists or with anticonvulsants, no evidence of differences was shown on dropouts and on other outcomes (abstinence from cocaine use, adverse events).

Authors' conclusions: At the current stage of evidence data do not support the efficacy of antidepressants in the treatment of cocaine abuse/dependence. Partially positive results obtained on secondary outcome measures, such as depression severity, do not seem to be associated with an effect on direct indicators of cocaine abuse/dependence. Antidepressants cannot be considered a mainstay of treatment for unselected cocaine abusers/dependents.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

1
1
Flow chart of studies.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Antidepressants vs placebo according to any definition, outcome: 1.1 Dropout.
5
5
Forest plot of comparison: 1 Antidepressants vs placebo according to any definition, outcome: 1.2 Retention in treatment as mean number of weeks in treatment.
6
6
Forest plot of comparison: 1 Antidepressants vs placebo according to any definition, outcome: 1.3 Abstinence, for at least three consecutive weeks.
7
7
Funnel plot of comparison: 1 Antidepressants vs placebo according to any definition, outcome: 1.1 Dropout.
8
8
Funnel plot of comparison: 1 Antidepressants vs placebo according to any definition, outcome: 1.3 Abstinence, for at least three consecutive weeks.
1.1
1.1. Analysis
Comparison 1 Antidepressants vs placebo according to any definition, Outcome 1 Dropout.
1.2
1.2. Analysis
Comparison 1 Antidepressants vs placebo according to any definition, Outcome 2 Retention in treatment as mean number of weeks in treatment.
1.3
1.3. Analysis
Comparison 1 Antidepressants vs placebo according to any definition, Outcome 3 Abstinence, for at least three consecutive weeks.
1.4
1.4. Analysis
Comparison 1 Antidepressants vs placebo according to any definition, Outcome 4 Abstinence as number of weeks of continuous abstinence.
1.5
1.5. Analysis
Comparison 1 Antidepressants vs placebo according to any definition, Outcome 5 Use of cocaine during the trial.
1.6
1.6. Analysis
Comparison 1 Antidepressants vs placebo according to any definition, Outcome 6 Craving for cocaine.
1.7
1.7. Analysis
Comparison 1 Antidepressants vs placebo according to any definition, Outcome 7 Addiction Severity Index (ASI) score.
1.8
1.8. Analysis
Comparison 1 Antidepressants vs placebo according to any definition, Outcome 8 Mood dichotomous measures.
1.9
1.9. Analysis
Comparison 1 Antidepressants vs placebo according to any definition, Outcome 9 Mood continuous measures.
1.10
1.10. Analysis
Comparison 1 Antidepressants vs placebo according to any definition, Outcome 10 Adverse events.
2.1
2.1. Analysis
Comparison 2 Antidepressants vs placebo for operationally defined cocaine dependence, Outcome 1 Dropout.
2.2
2.2. Analysis
Comparison 2 Antidepressants vs placebo for operationally defined cocaine dependence, Outcome 2 Retention in treatment.
2.3
2.3. Analysis
Comparison 2 Antidepressants vs placebo for operationally defined cocaine dependence, Outcome 3 Abstinence for at least three consecutive weeks.
2.4
2.4. Analysis
Comparison 2 Antidepressants vs placebo for operationally defined cocaine dependence, Outcome 4 Abstinence as number of weeks of continuous abstinence.
2.5
2.5. Analysis
Comparison 2 Antidepressants vs placebo for operationally defined cocaine dependence, Outcome 5 Use of cocaine during the trial.
2.6
2.6. Analysis
Comparison 2 Antidepressants vs placebo for operationally defined cocaine dependence, Outcome 6 Withdrawn due to adverse events.
3.1
3.1. Analysis
Comparison 3 Different class of antidepressants versus placebo, Outcome 1 Dropout.
3.2
3.2. Analysis
Comparison 3 Different class of antidepressants versus placebo, Outcome 2 Retention in treatment as mean number of weeks in treatment: tricyclics.
3.3
3.3. Analysis
Comparison 3 Different class of antidepressants versus placebo, Outcome 3 Abstinence for at least three consecutive weeks: tricyclics.
3.4
3.4. Analysis
Comparison 3 Different class of antidepressants versus placebo, Outcome 4 Abstinence as average number of weeks of continuous abstinence: tricyclics.
3.5
3.5. Analysis
Comparison 3 Different class of antidepressants versus placebo, Outcome 5 Use of cocaine during the trial: tricyclics.
3.6
3.6. Analysis
Comparison 3 Different class of antidepressants versus placebo, Outcome 6 Craving for cocaine.
3.7
3.7. Analysis
Comparison 3 Different class of antidepressants versus placebo, Outcome 7 Addidtion Severity Index (ASI) score, Drugs: SSRIs.
3.8
3.8. Analysis
Comparison 3 Different class of antidepressants versus placebo, Outcome 8 Mood continuous measures.
3.9
3.9. Analysis
Comparison 3 Different class of antidepressants versus placebo, Outcome 9 Adverse events.
4.1
4.1. Analysis
Comparison 4 Specific antidepressants versus placebo, Outcome 1 Dropout.
4.2
4.2. Analysis
Comparison 4 Specific antidepressants versus placebo, Outcome 2 Retention in treatment as mean number of weeks in treatment: desipramine.
4.3
4.3. Analysis
Comparison 4 Specific antidepressants versus placebo, Outcome 3 Abstinence for at least three consecutive weeks: desipramine.
4.4
4.4. Analysis
Comparison 4 Specific antidepressants versus placebo, Outcome 4 Abstinence as average number of weeks of continuous abstinence: desipramine.
4.5
4.5. Analysis
Comparison 4 Specific antidepressants versus placebo, Outcome 5 Use of cocaine during the trial: desipramine.
4.6
4.6. Analysis
Comparison 4 Specific antidepressants versus placebo, Outcome 6 Craving for cocaine.
4.7
4.7. Analysis
Comparison 4 Specific antidepressants versus placebo, Outcome 7 Mood continuous measures.
4.8
4.8. Analysis
Comparison 4 Specific antidepressants versus placebo, Outcome 8 Adverse events.
5.1
5.1. Analysis
Comparison 5 Antidepressants versus different class of other medications, Outcome 1 Dropout.
5.2
5.2. Analysis
Comparison 5 Antidepressants versus different class of other medications, Outcome 2 Craving for cocaine: antidepressants versus dopamine agonists.
5.3
5.3. Analysis
Comparison 5 Antidepressants versus different class of other medications, Outcome 3 Withdrawn due to adverse events: antidepressants versus dopamine agonists.
6.1
6.1. Analysis
Comparison 6 Different classes of antidepressants versus different classes of other medications, Outcome 1 Dropout: SSRIs versus anticonvulsants.
6.2
6.2. Analysis
Comparison 6 Different classes of antidepressants versus different classes of other medications, Outcome 2 Use of cocaine continuous measures: SSRIs versus anticonvulsants.
6.3
6.3. Analysis
Comparison 6 Different classes of antidepressants versus different classes of other medications, Outcome 3 Craving for cocaine: SSRIs versus anticonvulsants.
6.4
6.4. Analysis
Comparison 6 Different classes of antidepressants versus different classes of other medications, Outcome 4 Addiction Severity index (ASI) score, Drugs: SSRIs versus anticonvulsants.
7.1
7.1. Analysis
Comparison 7 Desipramine versus Amantadine, Outcome 1 Dropouts.
7.2
7.2. Analysis
Comparison 7 Desipramine versus Amantadine, Outcome 2 Abstinence, last week.
7.3
7.3. Analysis
Comparison 7 Desipramine versus Amantadine, Outcome 3 Craving for cocaine.
7.4
7.4. Analysis
Comparison 7 Desipramine versus Amantadine, Outcome 4 Mood (BDI).
8.1
8.1. Analysis
Comparison 8 Antidepressants plus psychosocial interventions vs placebo, Outcome 1 Dropout.
8.2
8.2. Analysis
Comparison 8 Antidepressants plus psychosocial interventions vs placebo, Outcome 2 Retention in treatment.
8.3
8.3. Analysis
Comparison 8 Antidepressants plus psychosocial interventions vs placebo, Outcome 3 Abstinence.
8.4
8.4. Analysis
Comparison 8 Antidepressants plus psychosocial interventions vs placebo, Outcome 4 Adverse events.
9.1
9.1. Analysis
Comparison 9 Antidepressants vs placebo participants also opioid dependence status, Outcome 1 Dropouts.
9.2
9.2. Analysis
Comparison 9 Antidepressants vs placebo participants also opioid dependence status, Outcome 2 Withdrawn due to adverse events.
10.1
10.1. Analysis
Comparison 10 Antidepressants vs placebo according to length of trial, Outcome 1 Dropout.
10.2
10.2. Analysis
Comparison 10 Antidepressants vs placebo according to length of trial, Outcome 2 Retention in treatment: more than six weeks of treatment.
10.3
10.3. Analysis
Comparison 10 Antidepressants vs placebo according to length of trial, Outcome 3 Abstinence for at least three consecutive weeks: more than six weeks of treatment.
10.4
10.4. Analysis
Comparison 10 Antidepressants vs placebo according to length of trial, Outcome 4 Withdrawn due to adverse events: more than six weeks of treatmentAdverse events.
11.1
11.1. Analysis
Comparison 11 Antidepressants vs placebo (excluding medication with questionable or uncertain antidepressant activity ), Outcome 1 Dropouts.
11.2
11.2. Analysis
Comparison 11 Antidepressants vs placebo (excluding medication with questionable or uncertain antidepressant activity ), Outcome 2 Retention in treatment as mean number of weeks in treatment.
11.3
11.3. Analysis
Comparison 11 Antidepressants vs placebo (excluding medication with questionable or uncertain antidepressant activity ), Outcome 3 Abstinence as number of weeks of continuous abstinence.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Kosten 1992 a {published data only}
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Cornelius 1998 {published data only}
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Gonzalez 2003 {published data only}
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Kosten 1992 b {published data only}
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Kosten 1992 c {published data only}
    1. Kosten TR, Gawin FH, Kosten TA, Morgan C, Rounsaville BJ, Schottenfeld R, et al. Six‐month follow‐up of short‐term pharmacotherapy for cocaine dependence. American Journal on Addictions 1992;1:40‐49.
Kosten 2005 {published data only}
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Leal 1994 {published data only}
    1. Leal J, Ziedonis D, Kosten T. Antisocial personality disorder as a prognostic factor for pharmacotherapy of cocaine dependence. Drug and Alcohol Dependence 1994;35:31‐5. - PubMed
Levin 2002 {published data only}
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Levin 2008 {published data only}
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McDowell 2000 {published data only}
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Milligan 2004 {published data only}
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Montoya 2002 {published data only}
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