Abuse of olanzapine by substance abusers.
Article Type: Case study
Subject: Olanzapine (Case studies)
Olanzapine (Dosage and administration)
Olanzapine (Chemical properties)
Olanzapine (Health aspects)
Drug abuse (Case studies)
Author: Reeves, Roy R.
Pub Date: 09/01/2007
Publication: Name: Journal of Psychoactive Drugs Publisher: Haight-Ashbury Publications Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2007 Haight-Ashbury Publications ISSN: 0279-1072
Issue: Date: Sept, 2007 Source Volume: 39 Source Issue: 3
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 172776817
Full Text: Abstract--Olanzapine has been used for over a decade for treatment of schizophrenia and bipolar disorder. The drug may have sedative properties for some patients, especially in large doses. The case reported here involves a 25-year-old male who abused olanzapine, both by itself and in combination with other drugs. Also described are the patient's reports of abuse of olanzapine by several of his acquaintances. The potential for abuse of olanzapine by substance abusers is discussed.

Keywords--drug abuse, olanzapine

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Olanzapine (Zyprexa[R]; Zydis[R]) is a thienobenzodiazepine which specifically blocks [5-HT.sub.2A] and D2 receptors and additionally blocks muscarinic ([M.sub.1]), [H.sub.1], [5-HT.sub.2C], [5-HT.sub.3], [5-HT.sub.6], [alpha]1, and [D.sub.4] receptors. It has greater affinity for [5-HT.sub.2] receptors than for [D.sub.2] receptors (Kelly, Conley & Carpenter 2005). Olanzapine has consistently been found to be significantly superior to placebo and comparable with, or superior to, haloperidol for the treatment of overall, positive, and negative symptoms of schizophrenia (Matza, Baker & Revicki 2005). The drug has been approved for treating acute mania, and has also been shown to possess antidepressant activity without destabilizing mood (Yaltham et al. 2005).

Olanzapine has a U.S. Federal Drug Administration approved dosing range of 10 to 20 mg/day but is sometimes used at higher doses. It is usually well tolerated. One of the drug's most common side effects is sedation. In acute phase trials, 39.1% of subjects taking between 12.5 and 17.5 mg of olanzapine daily experienced sedation (Beasley et al. 1996). Described here is the case of a young man who abused olanzapine, and his reports of abuse of the drug by several of his acquaintances.

CLINICAL CASE

Mr. A, a 25-year-old male, was court ordered to a drug treatment program because of his ongoing abuse of multiple drugs. He related that at about age 14 he began drinking alcohol and using marijuana. At about age 18 he began experimenting with other drugs and by age 21 was actively using cocaine, methamphetamines, and prescription narcotics, including oxycodone. He supported his habit by trafficking drugs. He was committed to treatment after becoming financially destitute and homeless.

Mr. A had also been given a diagnosis of bipolar disorder in his early twenties. He related several episodes of mania or hypomania, and he had experienced brief episodes of depression. At the time of his admission he was under treatment with olanzapine. Treatment had started with 10 mg daily. Because of his complaints to his physician of recurring mania this dosage had been gradually increased to 20 mg twice daily.

During his time in the drug treatment program Mr. A eventually disclosed that in addition to illicit drugs, he had frequently used olanzapine inappropriately. He found the sedation he experienced when taking the drug was "very relaxing" and described getting "a buzz" by taking 40 mg or more at a time. He admitted lying to his psychiatrist, exaggerating the severity of his manic symptoms to cause larger amounts of medication to be prescribed, and on a few occasions had claimed to have lost his prescription.

Mr. A also used olanzapine to augment or alter the effects of illicit drugs. He related that combining olanzapine and alcohol produced a pleasant euphoria for him, as did olanzapine taken with benzodiazepines. He also used olanzapine to blunt jitteriness and anxiey that occurred when he used cocaine, and on occasion took olanzapine to help "come down" from cocaine.

According to the patient, a number of his acquaintances who abused drugs were aware of these affects of olanzapine and used it in the same manner he did. He described it as a popular drug at parties, stating it was often referred to simply as "Zy." He related that olanzapine was sometimes bought, sold, or exchanged, usually for $4 to $6 per tablet. Although Mr. A had only abused the medication orally, he stated he had observed an individual who used it intravenously by dissolving a Zydis[R] tablet in water and then injecting it. Zydis[R] is the orally disintegrating form of olanzapine which dissolves within seconds of contact with saliva.

DISCUSSION

The information presented here might suggest that there exists a potential for the abuse of olanzapine by certain individuals who abuse other substances. Intentional misuse of psychotropic agents is not a new phenomenon. Besides medications with obvious abuse potential such as benzodiazepines and methyphenidate and other stimulants, abuse of a number of commonly prescribed psychiatric medications has been reported. Abuse of anticholinergic drugs was first reported in 1960 with the description of a patient who increased her trihexyphenidyl to achieve antidepressant and euphoriant effects (Bolin 1960). Since then reports of over 100 patients known to have abused anticholinergic drugs for stimulant, euphoriant, and hallucinogenic effects have been published and reviewed (Dilsaver 1988).

Tricyclic antidepressants are occasionally abused for their euphorogenic effects (Land, Pinsky & Salzman 1991) which may be related to their anticholinergic properties. For example, a reported case (Delilse 1990) involved a 24-year-old female with a history of alcohol and marijuana abuse who used increasing doses of amitriptyline such that she would achieve a "high" characterized by feelings of relaxation, giddiness, and contentment, and eventually confessed that she believed she was "addicted" to amitriptyline. Cohen, Hanbury and Stimmel (1978) investigated abuse of amitriptyline in patients enrolled in a methadone treatment program and found that 25% of the patients admitted to taking amitriptyline to achieve euphoria and 35% had drug screens positive for the drug. Hepburn and colleagues (2005) described three fatal cases in Scotland among intravenous drugs users who had high levels of tricyclic antidepressants post mortem, such that tricyclic abuse was believed to have contributed to their deaths. Recently, abuse of quetiapine for its sedative and anxiolytic effects (Pierre et al. 2004) has been reported to be prevalent in correctional facilities, with the abuse including intranasal snorting of pulverized tablets. Intranasal abuse of gabapentin by prison inmates with a prior history of cocaine dependence to obtain an altered mental state has also been reported (Reccoppa, Malcolm & Ware 2004).

Even if olanzapine should prove to have potential for abuse, it remains a useful medication for treatment of schizophrenic and bipolar patients, and has been demonstrated to be safe and effective in patients with schizophrenia and comorbid substance abuse disorders (Littrell et al. 2001). In some instances olanzapine may even possibly be useful for the treatment of substance abuse itself. Blockade of dopamine [D.sub.2] and serotonin [5-HT.sub.2] receptors could theoretically reduce the euphoric effects of cocaine and similar drugs and attenuate craving. Although an initial pilot clinical trial did not support the usefulness of olanzapine for treatment of cocaine dependency (Kampman et al. 2003), olanzapine has been shown to attenuate the reinforcing effects of cocaine in rats (Meil & Schechter 1997). A number of case reports (Sattar & Bhatia 2003; Sattar et al. 2003; Longo 2002) suggest that olanzapine may reduce craving and aid relapse prevention in patients with cocaine and alcohol dependency.

CONCLUSION

There appears to be some risk of abuse of olanzapine by certain substance abusers who are aware of its sedative and other pharmacological effects. This does not mean that olanzapine should be avoided in psychiatric patients with substance abuse any more than other medications such as quetiapine or gabapentin should be avoided because of anecdotal reports of their abuse. However, if patients demonstrate suspicious behavior related to olanzapine (e.g., appearing to seek larger than needed doses, losing prescriptions, etc.), the possibility of abuse of the medication should be considered.

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Journal of Clinical Psychopharmacology 23: 413-14. Yaltham, L.N.; Goldstein, J.M.; Vieta, E.; Bowden, C.L.; Grunze, H.; Post, R.M.; Suppes, T. & Calabrese, J.R. 2005. Atypical antipsychotics in bipolar depression: Potential mechanisms of action. Journal of Clinical Psychiatry 66 (Suppl 5): 40-48.

Roy R. Reeves, D.O., Ph.D.*

* Chief of Mental Health, G.V. (Sonny) Montgomery VA Medical Center; Professor of Psychiatry and Neurology, University of Mississippi School of Medicine, Jackson, MS.

Please address correspondence and reprint requests to Roy R. Reeves, D.O., Ph.D., Chief of Mental Health (11M), VA Medical Center, 1500 E. Woodrow Wilson Drive, Jackson, MS 39216. Phone: 601-368-4159, fax: 601-364-1395, email: roy.reeves@med.va.gov
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