Injectable Aripiprazole for Illicit Substance Cravings and Use
Based on the available evidence, injectable aripiprazole shows promise in reducing substance cravings, particularly for cocaine and alcohol, in patients with co-occurring psychiatric disorders, though data on actual substance use reduction remains limited.
Evidence for Craving Reduction
The most compelling evidence comes from recent systematic reviews and observational studies specifically examining aripiprazole in dual-diagnosis populations:
A 2024 systematic review found that 8 out of 12 studies demonstrated significant craving reduction after aripiprazole treatment in patients with severe mental illness and substance use disorders 1. The review included both oral and long-acting injectable formulations and showed clinical improvement in 11 of 12 studies 1.
A 2020 multicenter observational study of once-monthly LAI aripiprazole (400 mg/4 weeks) in 40 patients with schizophrenia and co-occurring substance use disorders demonstrated significant reductions in cocaine and alcohol dependence severity 2. After 6 months, 5 of 9 patients with cocaine use disorder and 3 of 16 patients with alcohol use disorder achieved complete abstinence 2.
An earlier 2005 open-label study switching 20 patients to aripiprazole found significant reductions in alcohol craving (p=0.003) and dollars spent on alcohol (p=0.042), as well as significant cocaine craving reduction (p=0.014) 3.
Mechanism and Rationale
Aripiprazole's unique pharmacology as a dopamine D2 receptor partial agonist may normalize dopaminergic neurotransmission involved in motivation, reward, and reinforcement of substance abuse 4. This differs from traditional dopamine antagonists or agonists previously studied for addiction 3.
Limitations and Clinical Caveats
The evidence base has significant limitations that must be acknowledged:
- Most studies have small sample sizes, high attrition rates, and lack placebo controls 3, 4
- The 2024 systematic review could not draw definitive conclusions about actual substance usage reduction or maintenance of abstinence 1
- A 2012 review concluded that given the low number of studies and frequent absence of comparators, clear conclusions about aripiprazole's efficacy in substance dependence cannot be drawn 4
- No major clinical guidelines (USPSTF, American College of Physicians, American Family Physician) specifically recommend aripiprazole for substance use disorders 5
Current Guideline Framework
The American College of Physicians emphasizes that evidence-based treatment for substance use disorders should include medication-assisted treatment components and counseling 5. However, these guidelines focus primarily on opioid use disorder treatments (naltrexone, buprenorphine, methadone) rather than aripiprazole 5.
Practical Clinical Approach
If considering LAI aripiprazole for a patient with co-occurring psychiatric illness and substance use disorder:
- Primary indication should be the psychiatric disorder (schizophrenia, schizoaffective disorder, bipolar disorder), with potential craving reduction as a secondary benefit 1, 2
- Use the standard dose of 400 mg once monthly, which was effective in the observational study 2
- Monitor for behavioral activation, akathisia, and mood destabilization, particularly early in treatment 6
- Expect potential craving reduction within weeks, but understand that complete abstinence is achieved in only a minority of patients 2
- Combine with counseling and comprehensive substance use disorder treatment rather than using aripiprazole as monotherapy 5
The most robust evidence exists for cocaine and alcohol use disorders specifically, not other illicit substances 1, 2, 3.