Pharmacotherapies for cannabis dependence

Kushani Marshall; Linda Gowing; Robert Ali; Bernard Le Foll

doi:10.1002/14651858.CD008940.pub2

Cochrane Database of Systematic Reviews

Pharmacothérapies pour la dépendance au cannabis

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DOI:

https://doi.org/10.1002/14651858.CD008940.pub2 Copiar DOI

Base de datos:

Cochrane Database of Systematic Reviews

Versión publicada:

17 diciembre 2014see what's new

Tipo:

Intervention

Etapa:

Review

Grupo Editorial Cochrane:

Grupo Cochrane de Alcohol y drogas

Copyright:

Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

Kushani Marshall

Discipline of Pharmacology, University of Adelaide, Adelaide, Australia
Linda Gowing

Correspondencia a: Discipline of Pharmacology, University of Adelaide, Adelaide, Australia

[email protected]
Robert Ali

Discipline of Pharmacology, University of Adelaide, Adelaide, Australia
Bernard Le Foll

Translational Addiction Research Laboratory, Centre for Addiction and Mental Health ; University of Toronto, Toronto, Canada

Contributions of authors

All authors contributed to the review concept and design. Kushani Marshall and Linda Gowing undertook literature searches, assessed studies for inclusion, and wrote a first draft of the text. Bernard Le Foll and Robert Ali provided comments at all stages of the review.

Sources of support

Internal sources

DASSA‐WHO Collaborating Centre in the Treatment of Drug and Alcohol Problems, Australia.

External sources

No sources of support supplied

Declarations of interest

Dr Le Foll is performing clinical research evaluating the utility of nabiximols for cannabis dependence treatment using drug supplies donated by GW Pharma. The research is supported by the Centre for Addiction and Mental Health, the Canadian Institute of Health Research (CSU 115548) and the National Institute On Drug Abuse of the National Institutes of Health (R21DA031906).

Acknowledgements

None

Version history

Published

Title

Stage

Authors

Version

2019 Jan 28

Pharmacotherapies for cannabis dependence

Review

Suzanne Nielsen, Linda Gowing, Pamela Sabioni, Bernard Le Foll

https://doi.org/10.1002/14651858.CD008940.pub3

2014 Dec 17

Pharmacotherapies for cannabis dependence

Review

Kushani Marshall, Linda Gowing, Robert Ali, Bernard Le Foll

https://doi.org/10.1002/14651858.CD008940.pub2

2011 Jan 19

Pharmacotherapies for cannabis withdrawal

Protocol

Kushani S Marshall, Linda Gowing, Robert Ali

https://doi.org/10.1002/14651858.CD008940

Differences between protocol and review

The original protocol focused on the management of cannabis withdrawal. When it became clear that very few studies considered withdrawal as a distinct phase, the review was broadened to include interventions to support cessation or reduction of cannabis use as well as management of withdrawal symptoms. The broadening of the review made the specification of "the portion of the scheduled treatment episode that is completed on average" less relevant; hence this was dropped from the review.

The original protocol stipulated the inclusion of studies that involve participants who are diagnosed according to DSM‐IV or ICD‐10 criteria as cannabis dependent, or where dependence is likely based on reported dose, duration and frequency of use (daily or multiple days per week). Given the qualifier of "where dependence is likely" the specification of DSM‐IV or ICD‐10 criteria would not have resulted in the exclusion of any included studies and was dropped from the methods of the review in the interests of simplicity.

The approach to heterogeneity specified in the protocol (use of a random‐effects model in the presence of statistical heterogeneity) was changed based on statistical advice received in the interim. The routine use of a random‐effects model is preferred and was the approach used for the review.

PICO

Population

Intervention

Comparison

Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Figure 1

Study flow diagram.

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Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 3

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Analysis 1.1

Comparison 1 Active medication versus placebo, Outcome 1 Number abstinent at end of treatment.

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Analysis 1.2

Comparison 1 Active medication versus placebo, Outcome 2 Number experiencing adverse effects.

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Analysis 1.3

Comparison 1 Active medication versus placebo, Outcome 3 Number withdrawn due to adverse effects.

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Analysis 1.4

Comparison 1 Active medication versus placebo, Outcome 4 Completion of treatment.

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Summary of findings for the main comparison. Abstinence at end of treatment

Active medication compared with 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	Active Medication
Number abstinent at end of treatment ‐ mixed action antidepressants	Study population		RR 0.82 (0.12 to 5.41)	179 (2 studies)	⊕⊝⊝⊝ very low^1,2
	250 per 1000	205 per 1000 (30 to 1000)
	Moderate
	233 per 1000	191 per 1000 (28 to 1000)
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.
¹ Significant heterogeneity between studies ² Studies small (< 300 participants in total)

Summary of findings for the main comparison. Abstinence at end of treatment

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Summary of findings 2. Withdrawal due to adverse effects

Active medication compared with 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	Active Medication
Number withdrawn due to adverse effects ‐ mixed action antidepressants	Study population		RR 1.44 (0.11 to 18.9)	179 (2 studies)	⊕⊝⊝⊝ very low^1,2
	11 per 1000	16 per 1000 (1 to 205)
	Moderate
	13 per 1000	19 per 1000 (1 to 246)
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.
¹ Studies differ in direction of effect without significant heterogeneity ² Very few events and small group sizes

Summary of findings 2. Withdrawal due to adverse effects

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Summary of findings 3. Completion of treatment

Active medication compared with 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	Active Medication
Completion of treatment ‐ THC preparations	Study population		RR 1.29 (1.08 to 1.55)	207 (2 studies)	⊕⊕⊕⊝ moderate²
	614 per 1000	792 per 1000 (663 to 951)
	Moderate
	618 per 1000	797 per 1000 (667 to 958)
Completion of treatment ‐ mixed action antidepressants	Study population		RR 0.93 (0.71 to 1.21)	169 (2 studies)	⊕⊕⊕⊝ moderate²
	573 per 1000	533 per 1000 (407 to 694)
	Moderate
	551 per 1000	512 per 1000 (391 to 667)
Completion of treatment ‐ SSRI antidepressants	Study population		RR 0.82 (0.44 to 1.53)	122 (2 studies)	⊕⊝⊝⊝ very low^1,2,3
	790 per 1000	648 per 1000 (348 to 1000)
	Moderate
	766 per 1000	628 per 1000 (337 to 1000)
Completion of treatment ‐ anticonvulsant and mood stabiliser	Study population		RR 0.78 (0.42 to 1.46)	75 (2 studies)	⊕⊝⊝⊝ very low^2,3
	405 per 1000	316 per 1000 (170 to 592)
	Moderate
	387 per 1000	302 per 1000 (163 to 565)
Completion of treatment ‐ atypical antidepressant (bupropion)	Study population		RR 1.06 (0.67 to 1.67)	92 (2 studies)	⊕⊝⊝⊝ very low^2,3
	429 per 1000	454 per 1000 (287 to 716)
	Moderate
	400 per 1000	424 per 1000 (268 to 668)
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.
¹ Significant heterogeneity between studies ² Studies small (< 300 participants in total) ³ One study at risk of attrition bias

Summary of findings 3. Completion of treatment

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Comparison 1. Active medication versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number abstinent at end of treatment Show forest plot	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 THC preparations	1	156	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.56, 2.30]
1.2 Mixed action antidepressants	2	179	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.12, 5.41]
1.3 SSRI antidepressants	1	52	Risk Ratio (M‐H, Random, 95% CI)	2.33 [0.68, 8.05]
1.4 Anticonvulsant and mood stabiliser	1	19	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.50, 2.34]
1.5 Buspirone	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.6 Atomoxetine	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.7 N‐acetylcysteine	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Number experiencing adverse effects Show forest plot	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 THC preparations	1	156	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.90, 1.46]
2.2 Mixed action antidepressants	1	76	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.55, 1.55]
2.3 SSRI antidepressants	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.4 Anticonvulsant and mood stabiliser	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.5 Buspirone	1	50	Risk Ratio (M‐H, Random, 95% CI)	1.23 [0.99, 1.53]
2.6 Atomoxetine	1	38	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.95, 1.46]
2.7 N‐acetylcysteine	1	116	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.59, 1.34]
3 Number withdrawn due to adverse effects Show forest plot	7		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 THC preparations	1	156	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.06, 15.31]
3.2 Mixed action antidepressants	2	179	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.11, 18.90]
3.3 SSRI antidepressants	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3.4 Anticonvulsant and mood stabiliser	1	50	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.07, 15.12]
3.5 Buspirone	1	50	Risk Ratio (M‐H, Random, 95% CI)	1.17 [0.08, 17.74]
3.6 Atomoxetine	1	38	Risk Ratio (M‐H, Random, 95% CI)	3.0 [0.13, 69.31]
3.7 N‐acetylcysteine	1	116	Risk Ratio (M‐H, Random, 95% CI)	3.0 [0.12, 72.15]
4 Completion of treatment Show forest plot	12		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 THC preparations	2	207	Risk Ratio (M‐H, Random, 95% CI)	1.29 [1.08, 1.55]
4.2 Mixed action antidepressants	2	169	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.71, 1.21]
4.3 SSRI antidepressants	2	122	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.44, 1.53]
4.4 Anticonvulsant and mood stabiliser	2	75	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.42, 1.46]
4.5 Buspirone	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.56, 1.77]
4.6 Atomoxetine	1	38	Risk Ratio (M‐H, Random, 95% CI)	1.29 [0.60, 2.74]
4.7 N‐acetylcysteine	1	116	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.83, 1.51]
4.8 Bupropion	2	92	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.67, 1.67]

Comparison 1. Active medication versus placebo

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Pharmacothérapies pour la dépendance au cannabis

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