Expert: Ivan Goldberg, M.D. - 4/5/2009

Question
I do some work work with families of those with mental illnesses.  Two families recently mention their adult child's docs prescribing Zyprexa for use prn.  Comments?  This is useful? acceptable? helpful?

Answer
Hi . . .

You do not mention bipolar disorder but for the purposes of this answer I will assume that we are discussing patients with bipolar disorder. The following is from a book I am in the process of finishing:

Q: Is there a role for antipsychotic medications in treating people with Bipolar Disorder who have never been psychotic?

A: In recent years psychiatrists have prescribed increasing amounts of antipsychotic medication for people with nonpsychotic mood disorders. A recent study found that 53% of patients with Bipolar II Disorder, who by definition have never had a psychotic episode have taken antipsychotic drugs as part of their treatment.

While antipsychotic medications may sometimes act as mood stabilizers or antidepressants, the possibility of serious, sometimes permanent, side effects accompanies their use. The two most serious of these are tardive dyskinesia (TD), and neuroleptic malignant syndrome. Weight gain, diabetes and increased blood lipids are other possible side effects. While anyone taking antipsychotic medications is at risk for developing TD, people with mood disorders are at much greater risk than people with schizophrenia.

While antipsychotic medications are frequently prescribed by our colleagues when treating patients with Bipolar Disorder who have never been psychotic we believe that, in general, psychiatrists should reserve antipsychotic medications for individuals experiencing a psychotic episode. After the psychosis remits, the antipsychotic medications should be stopped rather than continued indefinitely as is so commonly the current practice.

The manufacturers of the newer antipsychotic medications, by spending millions of dollars to change the “image” of these drugs, have fueled the dramatic increase in prescriptions for these medications. Many prestigious psychiatrists, after accepting thousands of dollars from drug companies, “educate” their less sophisticated colleagues to think of antipsychotic drugs as being mood stabilizers. Such antipsychotic medications have potentially severe side effects, including the number of suicide attempts, and should usually reserved for treating patients with psychoses.

The situation is made very difficult as the FDA has only approved quetiapine (Seroquel) and a combination of olanzapine and fluoxetine (Symbyax) for the treatment of individuals with Bipolar Depression.

Refs: Gao K, Ganocy SJ, Gajwani P, et al. A review of sensitivity and tolerability of antipsychotics in patients with bipolar disorder or schizophrenia: focus on somnolence. Journal of Clinical Psychiatry, 2008, 69, 302-309. Maina G, Albert U, Rosso G, et al. Olanzapine or lamotrigine addition to lithium in remitted bipolar disorder patients with anxiety disorder comorbidity: a randomized, single-blind, pilot study. Journal of Clinical Psychiatry, 2008, 69, 609-616. Malempati RN, Bond DJ, Yatham LN. Depot risperidone in the outpatient management of bipolar disorder: a 2-year study of 10 patients. International Clinics in Psychopharmacology, 2008, 23, 88-94. Derry S, Moore RA. Atypical antipsychotics in bipolar disorder: Systematic review of randomized trials. BMC Psychiatry, 2007, 16, 40. Han C, Lee MS, Pae CU, et al. Usefulness of long-acting injectable risperidone during 12-month maintenance therapy of bipolar disorder. Progress in Neuropsychopharmacology and Biological Psychiatry, 2007, 31, 1219-1223. Keck PE Jr, Calabrese JR, McIntyre RS, et al. Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: A 100-week, double-blind study versus placebo. Journal of Clinical Psychiatry, 2007, 68, 1480-1491. Smith LA, Cornelius V, Warnock A, et al. Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials. Bipolar Disorders, 2007, 9, 394-412. Yerevanian BI, Koek RJ, Mintz J. Bipolar pharmacotherapy and suicidal behavior Part 3: impact of antipsychotics. Journal of Affective Disorders, 2007,103, 23-28. Ehret MJ, Levin GM. Long-term use of atypical antipsychotics in bipolar disorder. Pharmacotherapy, 2006, 26, 1134-1147. Hellewell JS. A review of the evidence for the use of antipsychotics in the maintenance treatment of bipolar disorders. Journal of Psychopharmacology, 2006, 20 (2 Suppl), 39-45. Bowden CL. Atypical antipsychotic augmentation of mood stabilizer therapy in bipolar disorder. Journal of Clinical Psychiatry, 2005, 66 (Suppl 3), 12-19. Pini S, Abelli M, Cassano GB. The role of quetiapine in the treatment of bipolar disorder. Expert Opinion in Pharmacotherapy, 2006, 7, 929-940. Muzina DJ, Calabrese JR. Maintenance therapies in bipolar disorder: focus on randomized controlled trials. Australian and New Zealand Journal of Psychiatry, 2005, 39, 652-661. Tohen M, Chengappa KN, Suppes T, et al. Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabilizer v. mood stabilizer alone. British Journal of Psychiatry, 2004, 184, 337-345. Brambilla P, Barale F, Soares JC. Atypical antipsychotics and mood stabilization in bipolar disorder. Psychopharmacology (Berl), 2003, 166, 315-332. Gnanadesikan M, Freeman MP, Gelenberg AJ. Alternatives to lithium and divalproex in the maintenance treatment of bipolar disorder. Bipolar Disorders, 2003, 5, 203-216. Kusumakar V. Antidepressants and antipsychotics in the long-term treatment of bipolar disorder. Journal of Clinical Psychiatry, 2002, 63 (Suppl 10), 23-28. Brotman MA, Fergus EL, Post RM, et ala. High exposure to neuroleptics in bipolar patients: A retrospective review. Journal of Clinical Psychiatry, 2000, 61, 68-72. Ghaemi SN. New treatments for bipolar disorder: the role of atypical neuroleptic agents. Journal of Clinical Psychiatry, 2000, 61 (Suppl 14), 33-42. Gelenberg AJ, Hopkins HS. Antipsychotics in bipolar disorder. Journal of Clinical Psychiatry, 1996, 57 (Suppl 9), 49-52. Lancon C, Llorca PM. Clozapine in the treatment of refractory rapid cycling bipolar disorder. L’ Encephale, 1996, 22, 468-469. Puri BK, Taylor DG, Alcock ME. Low-dose maintenance clozapine treatment in the prophylaxis of bipolar affective disorder. British Journal of Clinical Practice, 1995, 49, 333-334. Littlejohn R, Leslie F, Cookson J. Depot antipsychotics in the prophylaxis of bipolar affective disorder. British Journal of Psychiatry, 1994, 165, 827-829. Serrnyak MJ, Woods SW. Chronic neuroleptic use in manic-depressive illness. Psychopharmacology Bulletin, 1993, 29, 375-381. Hunt N, Silverstone T. Tardive dyskinesia in bipolar affective disorder: A catchment area study. International Clinical Psychopharmacology, 1991, 6, 45-50. Prien RF, Gelenberg AJ. Alternatives to lithium for preventive treatment of bipolar disorder. American Journal of Psychiatry, 1989, 146, 840-848.

Q: You seem reluctant to use of antipsychotic medications as mood stabilizers despite the fact that treatment guidelines, from the American Psychiatric Association, for the treatment of individuals with Bipolar Disorder suggests their use. The FDA has also approved their use for the long-term management of people with Bipolar Disorder. Why are you so slow to prescribe antipsychotic medications as part of the long-term treatment of people with mood disorders?

A: We are slow to prescribe antipsychotic medications on a long-term basis for people with mood disorders because of the very real risk of tardive dyskinesia (See Part 3, P. XXX), neuroleptic malignant syndrome (See Part 3, P. XXX) weight gain, diabetes, increased cholesterol levels and the possible eventual development of heart disease(See Part 3, P. XXX).

Unfortunately many psychiatrists who sit on FDA review committees and who compile the American Psychiatric Association treatment guidelines accept money from drug manufacturers to consult with them, lecture to other physicians for them, and do research for them. As the conclusions of such psychiatrists are likely to be seriously biased by their financial involvements with the pharma¬ceutical industry, clinicians must question their recommendations.

The guidelines of the American Psychiatric Association will only become credible  guides to the therapy of individuals with psychiatric disorders when those who write such guidelines are individuals with no connections to the manufacturers of medications and therapeutic devices.

Refs: Holloway RG, Mooney CJ, Getchius TS, et al. Invited Article: Conflicts of interest for authors of American Academy of Neurology clinical practice guidelines. Neurology, 2008, 71, 57-63. Smulders YM, Thijs A. The influence of the pharmaceutical industry on treatment guidelines. Nederlands Tijdschrift voor Geneeskunde, 2007, 151, 2429-2431. Choudhry NK, Stelfox HT, Detsky AS. Relationships between authors of clinical practice guidelines and the pharmaceutical industry. Journal of the American Medical Association, 2002, 287, 612-617. Papanikolaou GN, Baltogianni MS, Contopoulos-Ioannidis DG, et al. Reporting of conflicts of interest in guidelines of preventive and therapeutic interventions. BMC Medical Research Methodology, 2001, 1, 3. Freemantle N, Johnson R, Dennis J, et al. Sleeping with the enemy? A randomized controlled trial of a collaborative health authority/industry intervention to influence prescribing practice. British Journal of Clinical Pharmacology, 2000, 49, 174-179.

Best regards . . .

Ivan
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