Table of Contents Author Guidelines Submit a Manuscript
Case Reports in Psychiatry
Volume 2014, Article ID 845145, 4 pages
Case Report

Treating Methamphetamine-Induced Resistant Psychosis with Clozapine

Mental Health Research Center, Faculty of Behavioral Sciences and Mental Health, Tehran Institute of Psychiatry, Iran University of Medical Sciences, Tehran, Iran

Received 14 July 2014; Revised 9 October 2014; Accepted 10 October 2014; Published 28 October 2014

Academic Editor: Shusuke Numata

Copyright © 2014 Ruohollah Seddigh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Methamphetamine-induced psychosis (MIP) in Iran has turned into a serious issue in terms of health and treatment, lacking any obvious treatment methods for its resistant cases. Aims of Case Report. In the present study, a number of two cases of treatment of MIP with clozapine, which were resistant to the treatment with other antipsychotics, have been reported. Both cases completely responded to the treatment in only 2 weeks and no signs of psychosis relapse were seen in an 8-9 follow-up. Conclusion. Because of its particular pharmacologic features, clozapine may be effective in treating MIP.

1. Introduction

During recent years, methamphetamine abuse has increased and turned into a serious concern [13]. Studies have shown that a chronic use of methamphetamine is accompanied by neurotoxicity, cognitive and psychiatric dysfunctions, and several performance-related troubles [4, 5] imposing huge costs on individuals, families, and society as well [6]. However, what has caused its abuse turning into a serious concern is psychosis induced by it, with it changing into a challenge for the health and treatment system in Iran [7]. Solely, a single experience of substance abuse among the individuals with an underlying psychotic disorder precipitate psychosis in 50–70% of such cases [8]; and among those individuals without any underlying factors, it may cause different types of short-term, long-term, and periodic psychosis or even those types being resistant to treatment with antipsychotic medications [5, 9, 10].

From treatment perspective, although some typical and atypical antipsychotics have been utilized in treating MIP [11], few studies have been conducted regarding resistant psychotic cases. For instance, some reports on the efficacy of electroconvulsive therapy (ECT) among these patients [12]. Moreover, this group of patients seems to have much heterogeneity in their responding to treatment [9].

The present report involves a treatment description of two patients affected by MIP, the symptoms of whom were only cured by taking clozapine. Our searches revealed that no use of clozapine has been reported in treating MIP yet.

2. Case Presentation

The First Patient. The first patient is a 34-year-old man, single, having primary education, a house painter. He began to consume opium, then heroin at the age of 20, and methamphetamine at the age of 25. During last 9 years, he was hospitalized 12 times due to MIP at psychiatry hospitals. In each hospitalization time, the symptoms were removed by different antipsychotic drugs in only 1-2 weeks; and their relapse again happened due to avoiding taking drugs and starting to consume it as well. In last 6 months, however, despite methamphetamine withdrawal, psychosis continued to remain. In psychiatric examinations, paranoid delusion and commanding auditory hallucinations were reported. Besides, the patient also complained about anxiety and occasional insomnia. He was totally alert answering our questions quite well. However, he was unaware of his psychotic states. In last 6 months, in spite of treatment with the following medications (each prescribed for 4 weeks), the symptoms were not removed: olanzapine: 15 mg daily; risperidone: 6 mg daily; and thiothixene: 15 mg daily.

Due to a failure in recovery from disease, the patient received 6 sessions of ECT. Each session caused seizure lasting averagely for 45 seconds (35–60 seconds) which was observed in the form of muscle contraction in patient’s bedside. Due to an occurrence of a long seizure (lasting for 130 seconds) in the 6th session and avoiding it through diazepam intravenous injection, ECT sessions were terminated. During these therapeutic sessions, no change was observed in patient’s psychotic state. Eventually, a treatment plan with clozapine (25 mg daily) was started and gradually titrated to 150 mg daily. As a result, psychosis was completely removed in only 2 weeks. In an 8-month follow-up and regarding clozapine consumption to be continued, no relapse in psychotic symptoms was observed. Concerning drug abuse, the patient was in “early full remission” based on DSM-IV-TR criteria despite the fact that he was not in a controlled environment. Thus, he completely withdrew from any substance abuse and returned to his work.

The patient’s familial background, regarding axis-I psychiatric disorders, was negative. Moreover, the patient himself had no background of axis-I psychiatric disorders prior to methamphetamine abuse. However, considering the existence of oppositional behaviors in his childhood and adolescence as well as his interview and results of questionnaire of Structured Clinical Interview for DSM-IV-TR Axis II (SCID-II), a diagnosis of antisocial personality disorder was evident for him. According to medical examinations, Complete Blood Count, tests of thyroid, liver and kidney functions, and tests on different hepatitis types and human immunodeficiency virus (HIV) as well as brain MRI were all normal. Besides, after the 6th session of ECT in neurologic counseling, no pathologic point was seen. Thus, it was merely advised to that ECT be terminated.

The Second Patient. The second patient is a 29-year-old man, single, having secondary education. He started substance abuse since he was 15 and has consumed all kinds of illegal drugs in Iran. However, he was affected by psychosis for the first time due to methamphetamine abuse since 6 months ago. In last 3 months, however, despite methamphetamine withdrawal, psychosis continued to remain. In the patient’s first visit to psychiatry clinic, persecutory delusion, reference delusion, somatic hallucinations (in a way that the patient felt an outer thing under his hand skin), and olfactory hallucinations (in a way that he felt the smell of opium) as well as anxiety, irritation, and loss of libido were seen. Due to being aggressive, the patient was hospitalized in psychiatric emergency department. Then, clonazepam (6 mg daily) was prescribed for him. In 24 hours, he was seen to be much calmer. However, he was unaware of his psychotic states. In last 6 months, despite treatment with the medications mentioned below (each lasting for 3 weeks), in spite of controlling aggression, psychosis was not removed: olanzapine: 15 mg daily; risperidone: 5 mg daily; quetiapine 600 mg daily; and haloperidol: 10 mg daily. Eventually, all drugs prescribed previously were avoided and clozapine (with a dosage of 100 mg daily), together with clonazepam (2 mg daily), started to be prescribed. One week after clozapine prescription, clonazepam was discontinued. In a 9-month follow-up and with the continuance of clozapine consumption, no signs of psychosis relapse were seen. Concerning drug abuse, he had no other abuse experience; and the patient returned to his work. So, he was in “early full remission” based on DSM-IV-TR criteria despite the fact that he was not in a controlled environment.

The patient’s familial and personal backgrounds, regarding axis-I psychiatric disorders were negative. However, a diagnosis of antisocial personality disorder was evident for him. Moreover, similar to the previous patient, all paraclinical examinations proved to be negative.

3. Discussion

Although MIP alleviates after a short period of time among numerous patients, it may last for several months in spite of stopping its abuse and taking antipsychotics as well; thus, pharmacologic therapy is indicated [9]. In many of studies, atypical antipsychotics have been prescribed in order to treat MIP, and the efficacy of such drugs as risperidone [13], olanzapine [14], quetiapine [15, 16], and aripiprazole [17] in treating it to some extent has been demonstrated. However, in the state of drug-resistant psychosis, there is no reliable evidence. For example one study has reported the positive influence of ECT in these cases [12]. In the present study, clozapine was prescribed due to the patients’ not responding to these treatment methods. Both patients continued to suffer from psychosis even after receiving at least 3 periods of treatment with nonclozapine antipsychotics. However, their symptoms were completely removed in only a short time period since taking clozapine.

From a neuroanatomical perspective, methamphetamine abuse with a low dosage causes damage to serotonergic pathways in areas of frontal cortex and hippocampus; and its high dosage abuse leads to some damage to striatum and parietal cortex [4, 18]. Considering neurotransmitters, methamphetamine leads to the release of high amounts of dopamine, norepinephrine, and serotonin in the brain, especially in striatum and its related areas [19]. But, in the case of its long-term abuse, it decreases not only the density of the above-mentioned neurotransmitters (especially dopamine) in the brain due to its neurotoxic effects [18] but also the number of D2 dopamine and dopamine transporter receptors [20]. Such effects may continue to occur even after a long withdrawal from abuse. On the other hand, a long-term abuse of methamphetamine may cause noradrenergic hyperactivity, individuals’ sensitivity to stress, and psychosis relapse [21]. Moreover, studies have shown that, in patients affected by a spontaneous relapse of psychosis after a long-term withdrawal, when they experience flashbacks, the norepinephrine and 3-methoxytyramine (the major metabolite of dopamine) blood levels are high in their blood [22]. The above profile represents the major excitatory effects of methamphetamine.

On the other hand, among antipsychotics, clozapine possesses unique features, compared to other antipsychotics. Clozapine has a high affinity towards 5-HT2 receptor blockade. This receptor has huge stimulating effects in the brain and is blocked to a high extent as the patient takes clozapine. Moreover, clozapine is a strong blocker of 5-HT3 as well as and adrenergic receptors [23]. Regarding this profile, clozapine seems to overcome adrenergic and serotonergic arousal seen in methamphetamine abuse. Thus, it may be considered as a treatment for MIP. Among other antipsychotics, such effects are also observed in aripiprazole [24]; however, according to very limited studies available, this drug just reduces the severity of psychosis in MIP [17]. Due to its unavailability, aripiprazole was not prescribed for the patients in this study.

Among clozapine effects, one other unique effect is its lower infinity towards D2 receptor blocks, compared to other antipsychotics in general, and toward many of D2 receptor blocks in mesolimbic areas, compared to those receptors in striatum areas [23]. This means that, considering neuropathology, mesolimbic areas may receive more importance than striatum areas do among those patients affected by MIP, with this demanding more future research on it.

The other important point made about the two patients in this report is their being in early full remission in an 8-9 follow-up. This means that clozapine may expert positive effect on some aspects related to methamphetamine abuse such as craving, those mood symptoms accompanied by psychosis, anxiety, and aggression. However, more controlled research needs to be done in an attempt to confirm this.


MIP:Methamphetamine-induced psychosis
ECT:Electroconvulsive therapy.


Written informed consent was obtained from the patients for publication of this report. A copy of the consent is available for review.

Conflict of Interests

The authors declare that they have no competing interests.

Authors’ Contribution

Ruohollah Seddigh and Amir-Abbas Keshavarz-Akhlaghi reported two cases and wrote them. Behnam Shariati designed the report and edited the paper. All authors read and approved the final paper.


  1. Z. Alam Mehrjerdi, “Crystal in Iran: methamphetamine or heroin kerack,” Daru, vol. 21, no. 1, p. 22, 2013. View at Publisher · View at Google Scholar
  2. O. Mehrpour, “Methamphetamin abuse a new concern in Iran,” Daru, vol. 20, no. 1, p. 73, 2012. View at Publisher · View at Google Scholar
  3. S. Momtazi and R. Rawson, “Substance abuse among Iranian high school students,” Current Opinion in Psychiatry, vol. 23, no. 3, pp. 221–226, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. W. J. Panenka, R. M. Procyshyn, T. Lecomte et al., “Methamphetamine use: a comprehensive review of molecular, preclinical and clinical findings,” Drug and Alcohol Dependence, vol. 129, no. 3, pp. 167–179, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. J. E. Zweben, J. B. Cohen, D. Christian et al., “Psychiatric symptoms in methamphetamine users,” The American Journal on Addictions, vol. 13, no. 2, pp. 181–190, 2004. View at Publisher · View at Google Scholar · View at Scopus
  6. N. Nicosia, R. L. Pacula, B. Kilmer, R. Lundberg, and J. Chiesa, “The economic cost of methamphetamine use in the United States, 2005,” DTIC Document, 2009. View at Google Scholar
  7. Z. A. Mehrjerdi, A. M. Barr, and A. Noroozi, “Methamphetamine-associated psychosis: a new health challenge in Iran,” DARU Journal of Pharmaceutical Sciences, vol. 21, article 30, 2013. View at Publisher · View at Google Scholar
  8. C. Curran, N. Byrappa, and A. McBride, “Stimulant psychosis: systematic review,” The British Journal of Psychiatry, vol. 185, pp. 196–204, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. K. Akiyama, “Longitudinal clinical course following pharmacological treatment of methamphetamine psychosis which persists after long-term abstinence,” Annals of the New York Academy of Sciences, vol. 1074, pp. 125–134, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. K. Akiyama, A. Saito, and K. Shimoda, “Chronic methamphetamine psychosis after long-term abstinence in Japanese incarcerated patients,” The American Journal on Addictions, vol. 20, no. 3, pp. 240–249, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Galanter and H. D. Kleber, The American Psychiatric Publishing Textbook of Substance Abuse Treatment, American Psychiatric Publishing, 2008.
  12. D. J. Grelotti, G. Kanayama, and H. G. Pope Jr., “Remission of persistent methamphetamine-induced psychosis after electroconvulsive therapy: presentation of a case and review of the literature,” The American Journal of Psychiatry, vol. 167, no. 1, pp. 17–23, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. L. Misra and L. Kofoed, “Risperidone treatment of methamphetamine psychosis,” The American Journal of Psychiatry, vol. 154, no. 8, article 1170, 1997. View at Google Scholar · View at Scopus
  14. S. J. Shoptaw, U. Kao, and W. W. Ling, “Treatment for amphetamine psychosis,” Cochrane Database of Systematic Reviews, no. 4, Article ID CD003026, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. G. Dore and M. Sweeting, “Drug-induced psychosis associated with crystalline methamphetamine,” Australasian Psychiatry, vol. 14, no. 1, pp. 86–89, 2006. View at Publisher · View at Google Scholar · View at Scopus
  16. V. Verachai, W. Rukngan, K. Chawanakrasaesin et al., “Treatment of methamphetamine-induced psychosis: a double-blind randomized controlled trial comparing haloperidol and quetiapine,” Psychopharmacology, vol. 231, no. 16, pp. 3099–3108, 2014. View at Publisher · View at Google Scholar · View at Scopus
  17. A. H. Sulaiman, J. S. Gill, M. A. Said, N. Z. Zainal, H. M. Hussein, and N. C. Guan, “A randomized, placebo-controlled trial of aripiprazole for the treatment of methamphetamine dependence and associated psychosis,” International Journal of Psychiatry in Clinical Practice, vol. 17, no. 2, pp. 131–138, 2013. View at Publisher · View at Google Scholar · View at Scopus
  18. T. E. Nordahl, R. Salo, and M. Leamon, “Neuropsychological effects of chronic methamphetamine use on neurotransmitters and cognition: a review,” Journal of Neuropsychiatry and Clinical Neurosciences, vol. 15, no. 3, pp. 317–325, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. S. J. Kish, “Pharmacologic mechanisms of crystal meth,” Canadian Medical Association Journal, vol. 178, no. 13, pp. 1679–1682, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. N. D. Volkow, L. Chang, G.-J. Wang et al., “Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex,” American Journal of Psychiatry, vol. 158, no. 12, pp. 2015–2021, 2001. View at Publisher · View at Google Scholar · View at Scopus
  21. K. Yui, K. Goto, S. Ikemoto, T. Ishiguro, and Y. Kamata, “Increased sensitivity to stress in spontaneous recurrence of methamphetamine psychosis: noradrenergic hyperactivity with contribution from dopaminergic hyperactivity,” Journal of Clinical Psychopharmacology, vol. 20, no. 2, pp. 165–174, 2000. View at Publisher · View at Google Scholar · View at Scopus
  22. K. Yui, K. Goto, and S. Ikemoto, “The role of noradrenergic and dopaminergic hyperactivity in the development of spontaneous recurrence of methamphetamine psychosis and susceptibility to episode recurrence,” Annals of the New York Academy of Sciences, vol. 1025, pp. 296–306, 2004. View at Publisher · View at Google Scholar · View at Scopus
  23. B. J. Sadock and V. A. Sadock, Kaplan and Sadock's Pocket Handbook of Clinical Psychiatry, Lippincott Williams & Wilkins, 2010.
  24. T. Futamura, S. Akiyama, H. Sugino, A. Forbes, R. D. McQuade, and T. Kikuchi, “Aripiprazole attenuates established behavioral sensitization induced by methamphetamine,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 34, no. 6, pp. 1115–1119, 2010. View at Publisher · View at Google Scholar · View at Scopus