Drug info - Abuse of olanzapine by substance abusers.(Case study).

[fnord]

Abuse of olanzapine by substance abusers.(Short Communication)(Case study).
Author(s):
Roy R. Reeves.
Source:
Journal of Psychoactive Drugs 39.3 (Sept 2007): p.297(3). (1715 words) From Academic OneFile.
Document Type:
Magazine/Journal
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Full Text :COPYRIGHT 2007 Haight-Ashbury Publications

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

**********

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.

REFERENCES

Beasley, C.M.; Tollefson, G.; Tran, P.; Saterlee, W.; Sanger, T.; Hamilton, S. & the Olanzapine HGAD Study Group. 1996. Olanzapine versus placebo and haloperidol. Acute phase results of the North American double-blind trial. Neuropsychopharmacology 14: 111-23.

Bolin, R.R. 1960. Psychiatric manifestations of artane toxicity. Journal of Nervous and Mental Disease 131: 256-60.

Cohen, M.J.; Hanbury, R. & Stimmel, B. 1978. Abuse of amitriptyline. Journal of the American Medical Aassociation 240: 1372-73.

Delilse, J.D. 1990. A case of amitriptyline abuse. American Journal of Psychiatry 147: 1377-78.

Dilsaver, S.C. 1988. Antimuscarinic agents as substances of abuse: A review. Journal of Clinical Psychopharmacology 8: 14-22.

Hepburn, S.; Harden, J.; Grieve, J.H.K. & Hiscox, J. 2005. Deliberate misuse of tricyclic antidepressants by intravenous drug users--case studies and report. Scottish Medical Journal 50 (3): 131-33.

Kampman, K.M.; Pettinati, H.; Lynch, K.G.; Sparkman, T. & O'Brien, C.P. 2003. A pilot trial of olanzapine for the treatment of cocaine dependence. Drug and Alcohol Dependence 70: 265-73.

Kelley, D.M.; Conley, R.R. & Carpenter, W.T. 2005. First episode schizophrenia. A focus on pharmacological treatment and safety considerations. Drugs 65: 1113-18.

Land, W.; Pinsky, D. & Salzman, C. 1991. Abuse and misuse of anticholinergic medications. Hospital & Community Psychiatry 42: 580-81.

Littrell, K.H.; Petty, R.G.; Hilligos, N.M.; Peabody, C.D.; & Johnson, C.G. 2001. Olanzapine treatment for patients with schizophrenia and substance abuse. Journal of Substance Abuse Treatment 21: 217-21.

Longo, L.P. 2002. Olanzapine for cocaine craving and relapse prevention in 2 patients [letter]. Journal of Clinical Psychiatry 63: 595-96.

Matza, L.S.; Baker, T.M. & Revicki, D.A. 2005. Efficacy of olanzapine and ziprasidonefor the treatment of schizophrenia: a systematic review. CNS Drugs 19: 499-515.

Meil, W.M. & Schechter, M.D. 1997. Olanzapine attenuates the reinforcing effects of cocaine. European Journal of Pharmacology 340 (1): 17-26.

Pierre, J.M.; Shnayder, I.G.; Wirshing, D.A. & Wirshing, W.C. 2004. Intranasal quetiapine abuse [letter]. American Journal of Psychiatry 161: 1718.

Reccoppa, L.; Malcolm, R. & Ware, M. 2004. Gabapentin abuse in inmates with prior history of cocaine dependency. American Journal on Addictions 13: 321-23.

Sattar, S.P. & Bhatia, S.C. 2003. Olanzapine for cocaine cravings and relapse prevention [letter]. Journal of Clinical Psychiatry 64: 969-70.

Sattar, S.P.; Grant, K.; Bhatia, S. & Petty, F. 2003. Potential use of olanzapine in treatment of substance dependence disorders [letter].

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: XXX


Source Citation:Reeves, Roy R. "Abuse of olanzapine by substance abusers.(Short Communication)(Case study)." Journal of Psychoactive Drugs 39.3 (Sept 2007): 297(3). Academic OneFile. Gale. Apollo Library. 27 Sept. 2008
<http://find.galegroup.com/ips/start.do?prodId=IPS>.


Gale Document Number:A172776817

[cybergenesis]

Meh I never think you can gain much insight into things from a single case study. There will be someone in the world capable of abusing any substance. Probably are people out there that smoke lettuce to get high.

[fnord]

Originally Posted by cybergenesis

. There will be someone in the world capable of abusing any substance. Probably are people out there that smoke lettuce to get high.

Well of course people are getting high off lettuce!.

[bryanbabylon]

Originally Posted by cybergenesis

Probably are people out there that smoke lettuce to get high.

Aaack, I have actually read about this a couple of times!!! How funny to come across this in a serious discussion!!!

[Felix Guattari]

SWiM has experienced a small amount of euphoria from olanzapine on the first uses, but tolerance to this effect quickly builds. I imagine one might be able to chase the euphoric effects by raising the dose but SWiM had no desire to try it. The starting dose for olanzapine for anxiety and panic attacks and schizophrenia is usually 5 mg and 10-15 for bipolar disorder. 40 mg, the dose mr. A was taking, would probably make most people stupid and sleepy, so I don't exactly see this having a huge amount of recreational potential - I would say it has more than seroquel, but far less than a benzo. Plus, overdosing could possibly cause akathisia, which is rather unpleasant.

It's starting to be used as a first-line treatment of panic/anxiety attacks in place of benzos and they hand it out in mental hospitals like candy. I suspect it might be untolerated in a greater percentage of patients than most benzos, but it lacks addictive potential.

[cybergenesis]

Honestly if people out there are looking for a drug to abuse their are few drugs I could recommend LESS than olanzapine.

Its useful only for producing sedation. So if you want to sleep, sure try it.

I have never experienced anything similar to a euphoric reaction on it (of doses up to 30mg). In fact at higher doses it tends to make me depressed and unmotivated.

It can cause quite pronounced weight gain. In the long term it can cause irreversible movement disorder. I don't think its use is justified in anxiety disorders, except maybe in the short term.

[humdroid]

'Scuse Y's ignorance, but he has always wondered something about tranquilizers, both benzo type ones, and the major ones, such as zyprexa.

Y has never used major tranquilisers, but was offered one on a comedown once, which he turned down.
He has used the odd benzo on a comedown, but prefers herbal aids, like valerian, and kanna.

Y wonders, because benzo type tranquilisers are addictive, and major ones are not, although major ones are much stronger, if Y had one anti-psychotic pill in his posession, could he not crush it, and just divide it up into many parts, and take one tiny part, say a sixteenth.

It may seem a silly question, and Y does not plan to abuse major tranquilisers, but if it were possible, would it not be preferable to benzos.

[cybergenesis]

They may be called major and minor tranquilizers but besides being sedative they have nothing in common. While benzo's are associated with potentially euphoric effects, the neuroleptics like olanzapine block dopamine in the brain. Dopamine is associate with pleasure and reward. By taking the major tranquilisers, you are if anything blocking your ability to get high or at least limiting it.

[Felix Guattari]

Olanzapine is, IMO, one of the better antipsychotics for comedowns, but any will work. Olanzapine is comparable to benzos for this purpose, though not quite as good. 25 mg of seroquel or 5 mg of zyprexa is a good place to start.

[eche05]

Thanks for posting. I'm working on a Ph.D. in psychiatry (not an english major, if you can tell ) and i'm writing a report on atypical antipsychotics, though am fairly acquanted with barbital/barbiturate/benzodiazepine typical sedative antipsycotics (secobarbital, ethylbarbital, alprazolam, anticonvulsants etc.)

This thienobenzodiazepine inhibits 5-hydroxytryptamine 2A (high doses of thiss neurochemical creates amphetamine psychosis-like symptoms), partial agonism of 5-hydroxytryptamine 1A and in some cases dopamine agonism. What's responsible for the anti-violence and dissociative/sedative properties of tienobenzodiazepine is the antagonism of muscanaric and nicotinic acetylcholine receptors (overactive function is similar to PCP induced violence via ACh receptor agonism).

Some researchers believe that D2 receptor antagonism, coupled with 5-HT2A receptor antagonism, is responsible for the "atypicality" of atypical anti-psychotics. Others believe that fast dissociation from the D2 receptor, allowing for better transmission of normal physiological dopamine surges, better explains the pharmacological evidence. The brain of a psychotic however, has different quantaties of neurochemicals recquiring different treatments per individual. To SWIM, though, this doesn't seem like much of an abusable drug. Or rather, not to appealing. SWIM likes the serotonnin and dopamine levels in his brain just the way they are.

eche05 added 3 Minutes and 51 Seconds later...

Originally Posted by Felix Guattari

Olanzapine is, IMO, one of the better antipsychotics for comedowns, but any will work. Olanzapine is comparable to benzos for this purpose, though not quite as good. 25 mg of seroquel or 5 mg of zyprexa is a good place to start.

Olanzapine is contradictory to seroquel and zyprexa, as it inhibits
5-hydroxytryptamine (serotonnin) whilst antidepressents exhibit selective serotonnin reuptake inhibitor physiologically. For comedowns, the treatment is drug-dependent with regards to serotonnin/dopamine activity. Benzodiazepines are a great place to start, with their sedative and anxylotic properties, specificly for amphetamines/stimulents (d-, l-, racemic, and cocaine derivatives such as methylphenidate/d-methylphenidate)

[Felix Guattari]

Olanzapine is contradictory to seroquel and zyprexa, as it inhibits
5-hydroxytryptamine (serotonnin) whilst antidepressents exhibit selective serotonnin reuptake inhibitor physiologically.

Could you clarify? I'm a little confused as to what that means.

Olanzapine is zyprexa/zydis.

I'm not sure what SSRIs have to do with anything here; while it's true that SSRIs act on the the serotonin transporter (by definition), I'm by no means convinced that this is the source of their therapeutic efficacy.

[Jatelka]

Originally Posted by eche05

though am fairly acquanted with barbital/barbiturate/benzodiazepine typical sedative antipsycotics (secobarbital, ethylbarbital, alprazolam, anticonvulsants etc.)

I am extremely confused. Non of the substances mentioned are typical antipsychotics, you have 2 barbiturates and a benzodiazepine mentioned

[eche05]

Originally Posted by Jatelka

I am extremely confused. Non of the substances mentioned are typical antipsychotics, you have 2 barbiturates and a benzodiazepine mentioned

I should clarify. I ment to add on to the list of acquainted substances, and there are reports of anti-anxiety medications in the treatment of psychotic episodes to reduce violence, and convulsions.

Barbitals and barbiturates are used typical antipsychotics due to their sedative, anticonvulsant, anesthetic, and hypnotic properties. Typicality of antipsychotics, though somewhat ambiguously defined, are the result of their heavily sedative pharmacology which would include the mentioned barbiturates.
www.en.wikiedpia.org/Secobarbital
http://en.wikipedia.org/wiki/Typical_antipsychotic
https://www.medicinescomplete.com/mc...Fmg-7000-n.htm

I assumed zyprexa was an SSRI (selective serotonnin reuptake inhibitor) antidepressent from the wording of the origonal post, when it is infact an atypical antipsychotic. My misunderstanding, as I mistook it for a generic similar to zoloft .
http://www.rxlist.com/zyprexa-drug.htm