Mechanism of action
The neuropharmacologic reasons for antipsychotics’ abuse potential are difficult to quantify. Quetiapine and olanzapine have been used to treat cocaine and alcohol abuse, and work perhaps by decreasing the dopamine reward system response to substance use.14,15 Quetiapine’s rapid dissociation from the dopamine receptor has been theorized to contribute to the drug’s abuse potential, possibly through relatively lower potency and decreased residence time at the dopamine receptor.14-16 This mechanism also contributes to quetiapine’s lower risk of extrapyramidal side effects, which make the drug easier to tolerate.
Although dopamine is a factor in substance abuse and treatment of psychotic disorders, other neuropharmacologic mechanisms must be considered. SGAs are theorized to cause dopamine release in the frontal cortex through effects as 5-HT1A agonists and 5-HT2A antagonists.16 Antagonism of α-adrenergic and histaminic receptors may account for these agents’ anxiolytic and sedative properties.8
Misuse of anticholinergic agents has been reported for >50 years.17 Psychiatric patients have been reported to increase use of anticholinergics for their movement side effects as well as hallucinogenic effects.18
Treatment
Regardless of the substance that patients abuse, the treatment goals are the same: to reduce use and achieve recovery. If a patient with psychosis is abusing an SGA, consider switching to an antipsychotic with less abuse potential. Another option is to limit the supply of the abused drug by prescribing smaller quantities or increase the frequency of follow-up visits to ensure compliant use.
Related Resources
- Substance Abuse and Mental Health Services Administration. www.samhsa.gov.
- Galanter M, Kelber HD. The American Psychiatric Publishing textbook of substance abuse treatment. Arlington, VA: American Psychiatric Publishing, Inc; 2008.
Drug Brand Names
- Aripiprazole • Abilify
- Diazepam • Valium
- Haloperidol • Haldol
- Hydrocodone/acetaminophen • Vicodin
- Olanzapine • Zyprexa
- Quetiapine • Seroquel
- Risperidone • Risperdal
Disclosure
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.