Antipsychotic medications for cocaine dependence

Blanca I Indave; Silvia Minozzi; Pier Paolo Pani; Laura Amato

doi:10.1002/14651858.CD006306.pub3

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Figure 1

Study flow diagram. Review update 2015.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1 Any antipsychotic versus placebo, Outcome 1 Dropouts.

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Analysis 1.2

Comparison 1 Any antipsychotic versus placebo, Outcome 2 Side effects.

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Analysis 1.3

Comparison 1 Any antipsychotic versus placebo, Outcome 3 Number of participants using cocaine during the treatment (as days/week by urine tests or self report).

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Analysis 1.4

Comparison 1 Any antipsychotic versus placebo, Outcome 4 Continuous abstinence (number of participants who maintained negative drug screens for 2 ‐ 3 weeks).

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Analysis 1.5

Comparison 1 Any antipsychotic versus placebo, Outcome 5 Craving (Brief Substance Craving Scale).

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Analysis 1.6

Comparison 1 Any antipsychotic versus placebo, Outcome 6 Severity of dependence (Addiction Severity Index).

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Analysis 1.7

Comparison 1 Any antipsychotic versus placebo, Outcome 7 Severity of dependence (Clinical Global Impression Scale).

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Analysis 1.8

Comparison 1 Any antipsychotic versus placebo, Outcome 8 Use of cocaine during the treatment (self‐reported as g/week).

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Analysis 1.9

Comparison 1 Any antipsychotic versus placebo, Outcome 9 Depression (Hamilton Depression Rating Scale).

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Analysis 2.1

Comparison 2 Risperidone versus placebo, Outcome 1 Dropouts.

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Analysis 2.2

Comparison 2 Risperidone versus placebo, Outcome 2 Severity of dependence (Addiction Severity Index).

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Analysis 3.1

Comparison 3 Olanzapine versus placebo, Outcome 1 Dropouts.

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Analysis 3.2

Comparison 3 Olanzapine versus placebo, Outcome 2 Side effects.

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Analysis 3.3

Comparison 3 Olanzapine versus placebo, Outcome 3 Use of cocaine during the treatment (self‐reported as days/week).

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Analysis 3.4

Comparison 3 Olanzapine versus placebo, Outcome 4 Use of cocaine during the treatment (self‐reported as days/past 30 days).

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Analysis 3.5

Comparison 3 Olanzapine versus placebo, Outcome 5 Continuous abstinence (participants who maintained negative drug screens throughout the treatment period ).

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Analysis 3.6

Comparison 3 Olanzapine versus placebo, Outcome 6 Craving (Brief Substance Craving Scale).

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Analysis 3.7

Comparison 3 Olanzapine versus placebo, Outcome 7 Severity of dependence (Addiction Severity Index).

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Analysis 3.8

Comparison 3 Olanzapine versus placebo, Outcome 8 Severity of dependence (Clinical Global Impression Scale).

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Analysis 3.9

Comparison 3 Olanzapine versus placebo, Outcome 9 Amount of of cocaine use during the treatment (self‐reported as dollars spent/past 30 days).

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Analysis 3.10

Comparison 3 Olanzapine versus placebo, Outcome 10 Depression (Hamilton Depression Rating Scale).

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Analysis 3.11

Comparison 3 Olanzapine versus placebo, Outcome 11 Anxiety (Hamilton Anxiety Rating Scale).

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Analysis 3.12

Comparison 3 Olanzapine versus placebo, Outcome 12 Withdrawal symptoms (Cocaine Selective Severity Assessment).

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Analysis 4.1

Comparison 4 Quetiapine versus placebo, Outcome 1 Dropouts.

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Analysis 4.2

Comparison 4 Quetiapine versus placebo, Outcome 2 Side effects.

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Analysis 4.3

Comparison 4 Quetiapine versus placebo, Outcome 3 Use of cocaine during the treatment (self‐reported as days/week).

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Analysis 4.4

Comparison 4 Quetiapine versus placebo, Outcome 4 Craving (Brief Substance Craving Scale).

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Analysis 4.5

Comparison 4 Quetiapine versus placebo, Outcome 5 Amount of of cocaine use during the treatment (self‐reported as g/week).

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Analysis 4.6

Comparison 4 Quetiapine versus placebo, Outcome 6 Amount of of cocaine use during the treatment (self‐reported as dollars spent/week).

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Analysis 4.7

Comparison 4 Quetiapine versus placebo, Outcome 7 Depression (Hamilton Depression Rating Scale).

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Analysis 4.8

Comparison 4 Quetiapine versus placebo, Outcome 8 Depression (Quick Inventory of Depressive Symptomatology).

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Analysis 4.9

Comparison 4 Quetiapine versus placebo, Outcome 9 Manic and hypomanic symptoms (Young Mania Rating Scale).

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Analysis 5.1

Comparison 5 Lamotrigine versus placebo, Outcome 1 Side effects.

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Analysis 6.1

Comparison 6 Reserpine versus placebo, Outcome 1 Dropouts.

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Analysis 6.2

Comparison 6 Reserpine versus placebo, Outcome 2 Craving (Brief Substance Craving Scale).

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Analysis 6.3

Comparison 6 Reserpine versus placebo, Outcome 3 Severity of dependence (Addiction Severity Index).

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Analysis 6.4

Comparison 6 Reserpine versus placebo, Outcome 4 Severity of dependence (Clinical Global Impression Scale).

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Analysis 6.5

Comparison 6 Reserpine versus placebo, Outcome 5 Depression (Hamilton Depression Rating Scale).

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Analysis 7.1

Comparison 7 Olanzapine versus haloperidol, Outcome 1 Dropouts.

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Analysis 7.2

Comparison 7 Olanzapine versus haloperidol, Outcome 2 Psychopathology (Positive and Negative Syndrome Scale).

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Analysis 7.3

Comparison 7 Olanzapine versus haloperidol, Outcome 3 Craving (Voris Cocaine Craving Questionnaire‐Intensity subscale).

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Analysis 8.1

Comparison 8 Olanzapine versus risperidone, Outcome 1 Dropouts.

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Analysis 8.2

Comparison 8 Olanzapine versus risperidone, Outcome 2 Depression (Hamilton Depression Rating Scale).

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Analysis 9.1

Comparison 9 Aripiprazol versus ropinirol, Outcome 1 Dropouts.

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Analysis 9.2

Comparison 9 Aripiprazol versus ropinirol, Outcome 2 Side effects.

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Analysis 9.3

Comparison 9 Aripiprazol versus ropinirol, Outcome 3 Craving (VAS Scale).

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Analysis 9.4

Comparison 9 Aripiprazol versus ropinirol, Outcome 4 Severity of dependence (Clinical Global Impression Scale).

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Analysis 9.5

Comparison 9 Aripiprazol versus ropinirol, Outcome 5 Amount of of cocaine use during the treatment (self‐reported as g/week).

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Summary of findings for the main comparison. Any antipsychotic versus placebo for cocaine dependence (Update)

Any antipsychotic versus placebo for cocaine dependence
Patient or population: people with cocaine dependence Settings: outpatients or inpatients Intervention: Any antipsychotic versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Any antipsychotic versus placebo
Dropouts Number of participants who dropped out from the study Follow‐up: mean 12 weeks	Study population		RR 0.75 (0.57 to 0.97)	397 (8 studies)	⊕⊕⊕⊝ moderate¹
	547 per 1000	411 per 1000 (312 to 531)
	Moderate
	500 per 1000	375 per 1000 (285 to 485)
Side effects Number of participants with at least i side effect Follow‐up: mean 12 weeks	Study population		RR 1.01 (0.93 to 1.10)	291 (6 studies)	⊕⊕⊝⊝ low²
	497 per 1000	502 per 1000 (462 to 546)
	Moderate
	465 per 1000	470 per 1000 (432 to 512)
Number of participants using cocaine during the treatment (as days/week by urine tests or self report) Number of participants that reported the use of cocaine during the treatment Follow‐up: mean 10 weeks	Study population		RR 1.02 (0.65 to 1.62)	91 (2 studies)	⊕⊕⊝⊝ low^3,4
	478 per 1000	488 per 1000 (311 to 775)
	Moderate
	596 per 1000	608 per 1000 (387 to 966)
Continuous abstinence (number of participants who maintained negative drug screens for 2 ‐ 3 weeks) Number of participants that maintained negative cocaine screens for at least 2 ‐ 3 weeks Follow‐up: mean 12 weeks	Study population		RR 1.30 (0.73 to 2.32)	139 (3 studies)	⊕⊕⊝⊝ low^1,5
	197 per 1000	256 per 1000 (144 to 457)
	Moderate
	129 per 1000	168 per 1000 (94 to 299)
Craving (Brief Substance Craving Scale) Brief Substance Craving Scale. Scale from: 0 to 4. Follow‐up: mean 11 weeks	The mean craving (brief substance craving scale) in the control groups was 2.39 score	The mean craving (Brief Substance Craving Scale) in the intervention groups was 0.13 higher (1.08 lower to 1.35 higher)		240 (4 studies)	⊕⊕⊝⊝ low^6,7
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹All the studies were at unclear risk of selection bias. ²One study was at high risk of selection bias, and the others at unclear risk. One study was at high risk of performance, detection bias and attrition bias, three at unclear risk. ³All the studies were at unclear risk of selection bias; one study was at unclear risk of performance and detection bias. ⁴Only two studies with 91 participants. ⁵Only three studies with 139 participants. ⁶All the studies were at unclear risk of selection, performance and attrition bias. One study was at high risk of attrition bias. ⁷High heterogeneity (I²: 85%).

Summary of findings for the main comparison. Any antipsychotic versus placebo for cocaine dependence (Update)

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Comparison 1. Any antipsychotic versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dropouts Show forest plot	8	397	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.57, 0.97]

2 Side effects Show forest plot	6	291	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.93, 1.10]

3 Number of participants using cocaine during the treatment (as days/week by urine tests or self report) Show forest plot	2	91	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.65, 1.62]

4 Continuous abstinence (number of participants who maintained negative drug screens for 2 ‐ 3 weeks) Show forest plot	3	139	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.73, 2.32]

5 Craving (Brief Substance Craving Scale) Show forest plot	4	240	Mean Difference (IV, Random, 95% CI)	0.13 [‐1.08, 1.35]

6 Severity of dependence (Addiction Severity Index) Show forest plot	4	211	Mean Difference (IV, Random, 95% CI)	0.01 [‐0.01, 0.04]

7 Severity of dependence (Clinical Global Impression Scale) Show forest plot	3	180	Mean Difference (IV, Random, 95% CI)	0.01 [‐0.38, 0.39]

8 Use of cocaine during the treatment (self‐reported as g/week) Show forest plot	2	72	Mean Difference (IV, Random, 95% CI)	‐0.54 [‐0.92, ‐0.16]

9 Depression (Hamilton Depression Rating Scale) Show forest plot	4	192	Mean Difference (IV, Random, 95% CI)	‐0.82 [‐3.19, 1.55]

Comparison 1. Any antipsychotic versus placebo

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Comparison 2. Risperidone versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dropouts Show forest plot	4	176	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.63, 1.04]

2 Severity of dependence (Addiction Severity Index) Show forest plot	1	31	Mean Difference (IV, Random, 95% CI)	0.03 [‐0.04, 0.10]

Comparison 2. Risperidone versus placebo

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Comparison 3. Olanzapine versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dropouts Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2 Side effects Show forest plot	2	79	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.92, 1.11]

3 Use of cocaine during the treatment (self‐reported as days/week) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

4 Use of cocaine during the treatment (self‐reported as days/past 30 days) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

5 Continuous abstinence (participants who maintained negative drug screens throughout the treatment period ) Show forest plot	2	79	Risk Ratio (M‐H, Random, 95% CI)	1.37 [0.71, 2.61]

6 Craving (Brief Substance Craving Scale) Show forest plot	2	61	Mean Difference (IV, Random, 95% CI)	1.33 [‐0.91, 3.58]

7 Severity of dependence (Addiction Severity Index) Show forest plot	2	61	Mean Difference (IV, Random, 95% CI)	0.03 [‐0.01, 0.07]

8 Severity of dependence (Clinical Global Impression Scale) Show forest plot	2	61	Mean Difference (IV, Random, 95% CI)	0.17 [‐0.51, 0.85]

9 Amount of of cocaine use during the treatment (self‐reported as dollars spent/past 30 days) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

10 Depression (Hamilton Depression Rating Scale) Show forest plot	2	61	Mean Difference (IV, Random, 95% CI)	1.34 [‐3.84, 6.52]

11 Anxiety (Hamilton Anxiety Rating Scale) Show forest plot	2	61	Mean Difference (IV, Random, 95% CI)	1.37 [‐3.02, 5.75]

12 Withdrawal symptoms (Cocaine Selective Severity Assessment) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

Comparison 3. Olanzapine versus placebo

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Comparison 4. Quetiapine versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dropouts Show forest plot	2	72	Risk Ratio (M‐H, Random, 95% CI)	0.64 [0.20, 2.03]

2 Side effects Show forest plot	2	72	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.77, 1.27]

3 Use of cocaine during the treatment (self‐reported as days/week) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

4 Craving (Brief Substance Craving Scale) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

5 Amount of of cocaine use during the treatment (self‐reported as g/week) Show forest plot	2	72	Mean Difference (IV, Random, 95% CI)	‐0.54 [‐0.92, ‐0.16]

6 Amount of of cocaine use during the treatment (self‐reported as dollars spent/week) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

7 Depression (Hamilton Depression Rating Scale) Show forest plot	1	12	Mean Difference (IV, Random, 95% CI)	‐3.67 [‐6.19, ‐1.15]

8 Depression (Quick Inventory of Depressive Symptomatology) Show forest plot	1	12	Mean Difference (IV, Random, 95% CI)	‐1.27 [‐9.61, 7.07]

9 Manic and hypomanic symptoms (Young Mania Rating Scale) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

Comparison 4. Quetiapine versus placebo

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Comparison 5. Lamotrigine versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Side effects Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

Comparison 5. Lamotrigine versus placebo

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Comparison 6. Reserpine versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dropouts Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2 Craving (Brief Substance Craving Scale) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

3 Severity of dependence (Addiction Severity Index) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

4 Severity of dependence (Clinical Global Impression Scale) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

5 Depression (Hamilton Depression Rating Scale) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

Comparison 6. Reserpine versus placebo

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Comparison 7. Olanzapine versus haloperidol

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dropouts Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2 Psychopathology (Positive and Negative Syndrome Scale) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

3 Craving (Voris Cocaine Craving Questionnaire‐Intensity subscale) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

Comparison 7. Olanzapine versus haloperidol

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Comparison 8. Olanzapine versus risperidone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dropouts Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2 Depression (Hamilton Depression Rating Scale) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

Comparison 8. Olanzapine versus risperidone

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Comparison 9. Aripiprazol versus ropinirol

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dropouts Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2 Side effects Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

3 Craving (VAS Scale) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

4 Severity of dependence (Clinical Global Impression Scale) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

5 Amount of of cocaine use during the treatment (self‐reported as g/week) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

Comparison 9. Aripiprazol versus ropinirol

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