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Treatments options for cocaine users

This page refers to the current evidence on the effectiveness of the available treatment options for cocaine and crack users. Information on the methodology used and the definition of terms can be found on the methodology page.

Date of last update: 05.2017 Next update: 10.2017

Effects of available treatments for cocaine users

Beneficial

Disulfiram for the treatment of cocaine dependence

There is limited evidence, at present supporting the clinical use of disulfiram for the treatment of cocaine dependence, but some ongoing studies might improve the results. The findings given here are from a systematic review by Pani et al. (2010) of seven RCTs (N=492).

Disulfiram was found to be statistically significantly better than a placebo in:

retaining patients in treatment (two studies, N=87 patients, RR 0.82, 95 % CI 0.66 to 1.03);
reducing cocaine use (no pooled results) (results from single studies showed that, one in four comparisons was in favour of disulfiram), number of weeks abstinence, 20 participants, WMD 4.50 (95 % CI 2.93 to 6.07).

Disulfiram was found to be statistically better than naltrexone in:

reducing dropouts (three studies, N=131 participants, RR 0.67, 95 % CI 0.45 to 1.01).

Disulfiram was found to be better than no pharmacological treatment in:

reducing cocaine use (one study, N=90 participants) maximum weeks of consecutive abstinence, WMD 2.10 (95 % CI 0.69 to 3.51); number of subjects achieving three or more weeks of consecutive abstinence (RR 1.88, 95 % CI 1.09 to 3.23).

Likely to be beneficial

Antidepressants to reduce cocaine use

A multi-treatment meta-analysis (MTM) of 11 studies (N=898, EMCDDA 2014) found antidepressants to be more effective than placebo in:

reducing use of cocaine (RR 0.72, 95 % CI 0.47 to 1.11)

Contingency management to reduce cocaine use

Contingency management was found in a systematic review (EMCDDA 2016, studies = 3, N=447) and a narrative review (Fischer et al., 2015) to be effective in:

reducing cocaine use (mean percentages of urine positive or negative for cocaine metabolites; two of the three studies reported statistically significant results in favour of CM)
improving abstinence (two of the three studies reported statistically significant results in favour of CM)

Psycho-social treatment (including contingency management) to retain crack-cocaine users in treatment and reduce use

A narrative review (Fischer et al., 2015), without meta-analysis, concluded that there is:

some evidence to support the effectiveness of contingency management in outcomes such as retention in treatment and behavioural outcomes, eg, reduce use, abstinence yet mixed evidence in relation to social outcomes, eg, housing and employment albeit in the short-term of treatment.

Psychosocial interventions to increase abstinence and reduce dropouts

Psychosocial interventions for psychostimulants were found in a systematic review (Minozzi et al., 2016, 52 RCTs, N= 6 923) when compared to no intervention to be effective in:

significantly increasing the longest period of abstinence (SMD: 0.48, 95 % CI 0.34 to 0.63, 10 studies, 1 354 participants, high quality evidence)
reducing the dropout rate (RR: 0.83, 95 % CI 0.76 to −0.91, 24 studies, 3 393 participants, moderate quality evidence);
increasing continuous abstinence at the end of treatment (RR: 2.14, 95 % CI 1.27 to −3.59, 8 studies, 1 241 participants, low quality evidence)
But did not significantly increase continuous abstinence at the longest follow-up (RR: 2.12, 95 % CI 0.77 to −5.86, 4 studies, 324 participants, low quality evidence).

The psychosocial interventions considered in the studies were: cognitive behavioural therapy (19 studies), contingency management (25 studies), motivational interviewing (5 studies), interpersonal therapy (3 studies), psychodynamic therapy (1 study), 12-step facilitation (4 studies).

Trade-off between benefits and harms

Withdrawal management for pregnant women with stimulant dependence

Evidence-based international guidelines (WHO, 2014) recommend using psychotropic medication in pregnant women to assist detoxification from stimulants, but should be reserved when specific symptoms emerge.
Harms to mother and fetus of ongoing use of psychostimulants use have been shown to be high, thus the potential benefits of this approach strongly outweigh the harms of providing psychopharmacological treatment of symptoms, if required, during psychostimulant withdrawal.

Unknown effectiveness

Antidepressants to reduce craving

A multi-treatment meta-analysis (MTM) of 9 studies (N=429, EMCDDA 2014) found no evidence for antidepressants when compared to placebo in:

reducing cocaine craving (RR - 0.03, 95 % CI -0.24 to 0.19)

Pharmacotherapy treatment options for crack-cocaine dependence

A narrative review (Fischer et al., 2015), without meta-analysis, concluded that, despite the availability of a numerous body of studies and agents tested:

no pharmacological option has proven to date to be effective.

Pyschosocial interventions versus comprehensive standard care for pregnant women for treatment and obstetrical outcomes

Psychosocial interventions were found in a systematic review (Terplan et al., 2015) to have no different effect than other interventions in:

improving retention in treatment (RR 0.99, 95 % CI 0.93 to 1.06, 9 studies, N=743)
improving abstinence (RR 1.14, 95 % CI 0.75 to 1.73, 3 studies, N=367)
reducing pre-term birth (RR 0.71, 95 % CI 0.34 to 1.51, 3 studies, N=264)
reducing low birth weight (RR 0.72, 95 % CI 0.36 to 1.43, 1 study, N=160)

Psychostimulants to reduce use and dropouts, to increase retention and improve abstinence

Psychostimulants were found in a systematic review (Castells et al., 2016, 26 RCTs, N= 2 366) to be not effective in:

reducing cocaine use (seven studies, including about 500 patients) (SMD 0.116, 95 % CI –0.027 to 0.2933);
retention in treatment (16 studies, including about 1.300 participants) (RR 0.971.00, 95 % CI 0.89 93 to 1.0506);
reducing the dropouts caused by adverse events (11 studies, including about 1.000 patients) (RD 0.0100, 95 % CI –0.02 01 to 0.0301)

The same review found very low quality evidence that psychostimulants improved sustained cocaine abstinence ((RR) 1.36, 95 % CI 1.05 to 1.77, P = 0.02).

Evidence of ineffectiveness

Anticonvulsants versus placebo for cocaine dependence

Anticonvulsants were found in a systematic review (Minozzi et al., 2015a) to have no different effect than placebo in:

reducing drop-outs (RR 0.95, 95 % CI 0.86 to 1.05, 17 studies, N=1695)
reducing use (RR 0.92, 95 % CI 0.84 to1.02, 9 studies, N=867)
reducing side effects (RR 1.39, 95 % CI 1.01 to 1.9, 8 studies, N=775)
reducing cravings (RR -0.25, 95 % CI -0.59 to 0.09, 7 studies, N=428)

Another systematic review with meta-analysis (Singh et al., 2016, 5 RCTs, N= 518) confirmed the results with no significant differences between topiramate and placebo in improving treatment retention (RR = 0.85; 95 % CI=0.60–1.22,P=0.38).

Antipsychotic medications for cocaine dependence

Antipsychotic drugs (risperidone, olanzapine, quetiapine, lamotrigine, aripiprazol, haloperidol and reserpine) were found in a systematic review (Indave et al., 2016) to have no different effect than placebo in:

reducing use (RR 1.02, 95 % CI 0.65 to 1.62, 2 studies, N=91)
sustaining abstinence (RR 1.30, 95 % CI 0.73 to 2.32, 3 studies, N=139)
reducing side effects (RR 1.39, 95 % CI 0.93 to 1.10, 6 studies, N=291)
reducing cravings (RR 0.13, 95 % CI -1.08 to 1.35, 4 studies, N=240)

The review found a slight reduction in dropouts when compared to placebo (RR 0.75, 95 % CI 0.57 to 0.97, 8 studies, N=397).

Dopamine agonists versus placebo for cocaine dependence

Dopamine agonists were found in a systematic review (Minozzi et al., 2015b) to have no different effect than placebo in:

reducing drop-outs (RR 1.04, 95 % CI 0.94 to 1.14, 20 studies, N=1656)
reducing adverse effects (RR 1.27, 95 % CI 0.66 to 2.44, 7 studies, N=252)
improving abstinence (RR 1.12, 95 % CI 0.85to 1.47, 11 studies, N=731)

Pharmacotherapy for pregnant women

Evidence-based international guidelines (WHO, 2014) do not recommend pharmacotherapy for routine treatment of dependence to stimulants and cannabis in pregnant women

References and definitions

List of references

Explanation of terms used

Below you can find definitions and further explanation for some of the terms used in this section of the Best practice portal. A more general glossary for the best practice portal is also available.

Affective-focused prevention intervention

A type of prevention intervention which aims to they aim to modify inner qualities (personality traits such as self-esteem and self-efficacy, and motivational aspects such as the intention to use drugs).

BA

Before-after (BA) study design

BAL

Blood alcohol level (BAL)

Beneficial

Interventions for which precise measures of the effects in favour of the type of intervention were found in systematic reviews of relevant studies. An intervention ranked as ‘beneficial’ is suitable for most patients/contexts. See the relevant module methodology page for further information.

CBA

Controlled before-after (CBA) study design. UCBA stands for Uncontrolled before-after study design.

CBT

Cognitive behavioral therapy is an individual based intervention occurring in three stages. Phase 1 is aimed at determining and prioritizing the patient’s problems and constructing the treatment contract. Phase 2 is aimed at increasing coping competence and reducing risky behaviors. Phase 3 focuses on relapse prevention. Each session is administered once per week over a period of 4-6 months with 60- to 90-minute sessions (Beck AT, Wright FW, Newman CF, Liese B. Cognitive Therapy of substance abuse. New York: Guilford Press, 1993).

CCT

Controlled clinical trials (CCT)

Cohort study

A cohort study is a type of observational study that follows a group of people (i.e. a cohort) over time. In a prospective cohort study, the cohort is formed and then followed over time. In a retrospective cohort study, data is gathered for a cohort that was formed sometime in the past.

Confidence Interval (CI)

The Confidence Interval (CI) is a measure of the precision (or uncertainty) of study results. It is the interval that most likely includes the true value of the parameter we are calculating, where 'most likely' is taken by common usage to be a 95% probability. Thus the current expression of '95 % CI'. A wide CI indicates less precise estimates of effect and vice versa.

Practical interpretation

If the RR (the relative risk) = 1, or the CI (the confidence interval) = 1, then there is no significant difference between treatment and control groups
If the RR > 1, and the CI does not include 1, events are significantly more likely in the treatment than the control group
If the RR < 1, and the CI does not include 1, events are significantly less likely in the treatment than the control group

CPS

Current population survey (CPS)

Cross-sectional study

A cross-sectional study is a study employing a single point of data collection for each participant or system being studied.They are usually conducted to estimate the prevalence of the outcome of interest for a given population at a given point in time.

Evidence of ineffectiveness

Interventions that gave negative results if compared with a standard intervention or no intervention, for example. See the relevant module methodology page for further information.

Additional information for prevention
For ethical reasons this category in prevention should be considered as interventions with negative and undesired (iatrogenic) effect.

IP

Individual psychotherapy is a standard individual treatment based on counseling and motivational interviewing and focused on substance use triggers and strategies for relapse prevention. It includes elements of cognitive-behavioral therapy (CBT).

IQR

Interquartile range (IQR) - also called the midspread or middle fifty - is a measure of statistical dispersion. It is a trimmed estimator, defined as the 25% trimmed mid-range, and is the most significant basic robust measure of scale.

ITS

Intermittent time series design (ITS)

Knowledge-focused prevention intervention

A type of prevention intervention which aims to to enhance knowledge of drugs, and drug effects, and consequences.

Likely to be beneficial

Interventions that were shown to have limited measures of effect, that are likely to be effective but for which evidence is limited. An intervention ranked as ‘likely to be beneficial’ is suitable for most contexts/patients, with some discretion. See the relevant module methodology page for further information.

Number Needed to Treat (NNT)

The Number Needed to Treat (NNT)indicates the number of patients that needs to be treated to obtain one respondent patient. Numerically the NNT is the reciprocal of the difference between the proportion of events in the experimental and the comparison group (absolute risk reduction). Taking into consideration that the ideal NNT would be 1 (the unreal situation in which every single patient succeeded) it is easily understood that a NNT value close to 3 or 4 would be very good.

Adjusted Odds Ratio (AOR)

The Adjusted Odds Ratio is a way of comparing whether the probability of a certain event is the same between two groups, yet they are calculated adjusting for or controlling for other possible contributions from other variables (tipically demographic variables) in the model. An AOR equal to 1 implies that the the event is equally probable in both groups. An AOR greater than 1 implies that the event is more likely in the first group. An AOR less than 1 implies that the event is less likely in the first group.

Odds Ratio (OR)

The Odds Ratio is a way of comparing whether the probability of a certain event is the same between two groups. Like the Relative Risk, an OR equal to 1 implies that the the event is equally probable in both groups. A OR greater than 1 implies that the event is more likely in the first group. A OR less than 1 implies that the event is less likely in the first group. In medical research, the odds ratio is commonly used for case-control studies, as odds, but not probabilities, are usually estimated. Relative risk is used in randomized controlled trials and cohort studies.

p value

A p-value is a measure of how much evidence we have against the null hypothesis. The null hypothesis represents the hypothesis of no change or no effect. The smaller the p-value, the more evidence we have against the null hypothesis thus it is more likely that our sample result is true. Traditionally, researchers will reject a null hypothesis if the p-value is less than 0.05.

RBS

Responsible beverage service (RBS)

RCT

Randomised controlled trial (RCT)

Relative Risk (RR)

The Relative Risk (RR) is used to compare the risk in the two different groups of people, i.e. treated and control groups to see if belonging to one group or another increases or decreases the risk of developing certain outcomes. This measure of effect will tell us the number of times an outcome is more likely (RR > 1) or less likely (RR < 1) to happen in the treatment group compared with the control group.

Practical interpretation

If the RR (the relative risk) = 1, or the CI (the confidence interval) = 1, then there is no significant difference between treatment and control groups
If the RR > 1, and the CI does not include 1, events are significantly more likely in the treatment than the control group
If the RR < 1, and the CI does not include 1, events are significantly less likely in the treatment than the control group

Trade-off between benefits and harms

Interventions that obtained measures of effects in favour of the intervention, but that showed some limitations or unintended effects that need to be assessed before providing them. See the relevant module methodology page for further information.

Unknown effectiveness

Interventions for which there are not enough studies or where available studies are of low quality (with few patients or with uncertain methodological rigour), making it difficult to assess if they are effective or not. Interventions for which more research should be undertaken are also grouped in this category.

Additional information for prevention
For prevention interventions, this is also known as 'zero effect'.

Skill-focused prevention intervention

A type of prevention intervention which aims to enhance students’ abilities in generic skills, refusal skills and safety skills.

Standardised Mean Difference (SMD)

The Standardised Mean Difference (SMD) is the difference in means divided by a standard deviation. Note that it is not the standard error of the difference in means (a common confusion). The standardized mean difference has the important property that its value does not depend on the measurement scale. It may be useful if there are several trials assessing the same outcome, but using different scales.

z score (Standard Score): The z-score (aka, a standard score) indicates how many standard deviations an element is from the mean of the population.

About cocaine use

Case definition

The Diagnostic and statistical manual, 5th edition, describes cocaine use disorder as characterized by a problematic pattern of cocaine use leading to clinically significant impairment or distress. Typically includes a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and a physical withdrawal state.

Overall, cocaine remains the second most used illicit drug in Europe, after cannabis, though levels of use vary greatly between countries. It is estimated that around 13 million Europeans have used it at least once in their lifetime, on average 3.9 % of adults aged 15–64 years.

Aetiology

Cocaine clients have one of the largest male to female ratios (five men for every woman) and one of the highest mean ages (around 32 years) among drug treatment clients. This is particularly the case in some countries with large numbers of primary cocaine clients, especially Italy where the sex ratio is 8:1 and the mean age 35 years.

Almost half of cocaine users start using the drug before the age of 20, and 88 % before the age of 30. Long time lags (9–12 years) between first cocaine use and first treatment entry are reported in Spain and Italy.

Prevalence

Cocaine use in Europe remains concentrated in western countries, where the trend is generally stable or still increasing. However, there is evidence of the further diffusion of the drug into other countries. Treatment demands related to cocaine are also growing. From the evidence available, it is possible to conclude that current consumption levels remain high and are not diminishing in established areas, and are continuing to grow elsewhere. In 2007 cocaine was the principal drug reported by users entering treatment in outpatient by the 18 % of the clients.

Treatment

In Europe, public drug treatment facilities are mostly oriented towards the needs of opioid users, and those focusing on the treatment of cocaine users are rare and often private. Some countries (e.g. Ireland, Italy, Spain), however, have implemented strategies or treatment programmes targeting cocaine users, and France is in the process of developing such programmes. The heterogeneity of cocaine users, and of their problems and needs, complicates the organisation and delivery of treatment services to those who need them.

Outcomes

Treatments may not be effective in achieving all the desired outcomes, these outcomes are prioritised.

Primary outcomes

Retention in treatment (observational studies* showed that people in treatment are less likely to take risks, and to be involved in crimes).
Acceptability of the treatment, side effects experienced during the treatment.
Use of cocaine.

* studies such as National Treatment Outcome Research Study – NTORS, Australian Treatment Outcome Study – ATOS

Prognosis

Two main groups of cocaine clients have been identified in treatment — socially integrated individuals using powder cocaine, and a more marginalised group of clients using cocaine (often crack-cocaine) in combination with opioids.

References

American Psychiatric Association (2000), Diagnostic and statistical manual of mental disorders, 4th edition, text revision, American Psychiatric Association, Washington, DC.

EMCDDA statistical bulletin

EMCDDA , Annual report: the state of the drugs problem in Europe, EMCDDA, Lisbon

Minozzi, S., Amato, L., Davoli, M., et al. (2008), ‘Anticonvulsants for cocaine dependence’, Cochrane Database of Systematic Reviews, Issue 2.

Silva de Lima, M., Farrell, M., Lima Reisser, A. A. R. L., Soares, B. (2010), ‘Antidepressants for cocaine dependence’, Cochrane Database of Systematic Reviews, Issue 2.

Soares, B., Lima Reisser, A. A. R. L., Farrell, M. and Silva de Lima, M. (2010), ‘Dopamine agonists for cocaine dependence’, Cochrane Database of Systematic Reviews, Issue 2.

Ongoing studies

About the EMCDDA

The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is the reference point on drugs and drug addiction information in Europe. Inaugurated in Lisbon in 1995, it is one of the EU's decentralised agencies. Read more >>