Expert: Ivan Goldberg, M.D. - 10/24/2008

Question
Hi. I have Bipolar I with psychotic features and need to be on an antipsychotic. I currently take only 30 mg of Abilify/day. I used to be on Risperdal and Lithium and gained a tremendous amount of weight. I switched to Abilify and started working out 30-50 minutes 5 times per week and eating a reduced calorie diet. It has been a month and I am still gaining weight.

I am wondering if Geodon is less likely to cause weight gain than Abilify and if Geodon is as/or more effective than Abilify in controlling psychotic symptoms.

I know my doctor is open to finding the right medication for me, but I don't think she wants me to take Topomax or Metformin just to help with weight loss.

Answer
Hi Courtney . . .

There is no evidence de that Geodon is more or less effective or more or less likely to cause weight gain. Of the newer antipsychotics it is very clear that the two of them are the ones least likely to increase weight cholesterol, etc.

You don't mention of you are only on the Abilify or if you are also taking other medications ghat might contribute to the weight gain.

I don't understand your doctor's reluctance to use Topamax and/or metformin to help you reduce your weight. I find that those medications, especially when used together, are often very helpful to prevent or reverse weight gain caused by psychopharmaca.


There is an old antipsychotic that I frequently prescribe when weight gain has resulted form all of the newer antipsychotics. The oldie but goodie is molindone (Moban) and its use is frequently accompanied by weight loss. Below are a few abstracts on molindone and weight loss:

1: Cochrane Database Syst Rev. 2007 Jan 24;(1):CD002083.

Update of:
   Cochrane Database Syst Rev. 2000;(2):CD002083.

Molindone for schizophrenia and severe mental illness.

Bagnall A, Fenton M, Kleijnen J, Lewis R.

Leeds Metropolitan University, School of Health & Community Care, Calverley Street, Leeds, UK, LS1 3HE. A.Bagnall@leedsmet.ac.uk

BACKGROUND: Antipsychotic therapy is the mainstay of treatment for people with schizophrenia. In recent years new or atypical antipsychotics have been introduced. These are less likely to produce movement disorders and raise serum prolactin.Researchers have suggested that molindone should be classified as an
atypical antipsychotic. OBJECTIVES: To determine the effects of molindone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: For the original search we searched the following databases: Biological Abstracts (1980-1999), The Cochrane
Library CENTRAL (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), CINAHL (1982-1999), EMBASE (1980-1999), MEDLINE (1966-1999),LILACS (1982-1999), PSYNDEX (1977-1999), and PsycLIT (1974-1999). We also searched pharmaceutical databases on the Dialog Corporation Datastar and Dialog and the references of all identified studies for further trials. Finally, we contacted the manufacturer of molindone and the authors of any relevant
trials.For the update of this review, we searched The Cochrane Schizophrenia Group's Trials Register (August 2005). SELECTION CRITERIA: We included all randomised controlled trials that compared molindone to other treatments for schizophrenia and schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently and analysed on an intention to treat basis
calculating, for binary data, the fixed effect relative risk (RR), their 95% confidence intervals (CI), and the number needed to treat or harm (NNT or NNH). We excluded data if loss to follow up was greater than 50%. MAIN RESULTS: We included fourteen studies. Duration ranged from very short (10 days) studies of the intramuscular preparation, to trials lasting over three months. For measures of global assessment, available data do not justify any conclusions on the comparative efficacy of molindone and placebo. When compared to other typical antipsychotics we found no evidence of a difference in effectiveness (doctors' 4 RCTs n=150, RR 1.13, CI 0.69 to 1.86; nurses 4RCTs n=146, RR 1.23, CI 0.82 to 1.86). Molindone is no more or less likely than typical drugs to cause movement disorders, but it does cause significantly more weight loss (2RCTs n=60 RR 2.78, CI 1.10 to 6.99, NNH 5 CI 2 to 77). AUTHORS' CONCLUSIONS: The strength of the evidence relating to this compound is limited, owing to small sample size, poor study design, limited outcomes and incomplete reporting. Molindone may be an effective antipsychotic but its adverse effect profile does not differ
significantly from that of typical antipsychotics (apart from the event of weight loss). Data from this review suggest, at present, there is no evidence to suggest that it may have an atypical profile.

Publication Types:
   Meta-Analysis
   Review

PMID: 17253473 [PubMed - indexed for MEDLINE]

2: Drug Saf. 1996 May;14(5):329-42.

Bodyweight change as an adverse effect of drug treatment. Mechanisms and
management.

Pijl H, Meinders AE.

Department of General Internal Medicine, Leiden University Hospital, The Netherlands.

A number of drugs are capable of changing bodyweight as an adverse effect of their therapeutic action. Bodyweight gain is more of a problem than bodyweight loss. As bodyweight gain during drug treatment for any kind of disease may be the reflection of improvement of the disease itself, we will try to separate these
effects from those due to drug-induced alterations of the mechanisms regulating bodyweight. Bodyweight gain may jeopardise patient compliance to the prescribed regimen and it may pose health risks. The body mass index (BMI) is determined by dividing bodyweight in kilograms by height in metres squared. A BMI of > or = 27 kg/m2 warrants therapeutic action; nutritional counselling and programmed
physical exercise can be used as a basis. In general, if basic therapeutic measures are unsuccessful at controlling bodyweight gain then a change of drug might help. Finally, an anoretic drug may serve to support dietary measures. However, safety and efficacy has been demonstrated for only a few anorectic drugs when used as an adjunct to caloric restriction in the treatment of drug-induced
obesity. Bodyweight is determined by complex mechanisms regulating energy balance. A number of neurotransmitter systems acting in several hypothalamic nuclei are pivotal to the regulation of body fat stores. Most drugs that are capable of changing bodyweight interfere with these neurotransmitter systems. The
increment is dependent on the type and dose of the drug concerned. Some antidepressant drugs induce bodyweight gain, which may amount to 20 kg over several months of treatment. Monoamine oxidase inhibitors appear to cause less bodyweight change than tricyclic antidepressants. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors cause bodyweight loss instead of bodyweight gain. Lithium may cause large increases in bodyweight. Generally
speaking, the bodyweight change induced by antipsychotics is more often of clinical significance than the bodyweight change associated with the use of antidepressants. Again, the changes of bodyweight are dependent upon the type and dose of the antipsychotic drug involved. Although almost all antipsychotics induce bodyweight gain, molindone and loxapine appear to induce bodyweight loss. Anti-convulsants, especially valproic acid (sodium valproate) and carbamazepine, induce bodyweight gain in a considerable percentage of patients. Treatment with corticosteroids is associated with dose-dependent bodyweight gain in many patients. Corticosteroid-induced obesity aggravates other corticosteroid-associated health risks. Insulin therapy in diabetic patients usually increases bodyweight. Finally, sulphonurea derivatives, antineoplastic agents used for the treatment of breast cancer and several drugs used in migraine
prophylaxis may cause bodyweight gain as well.

Publication Types:
   Review

PMID: 8800628 [PubMed - indexed for MEDLINE]

3: Schizophr Bull. 1995;21(3):463-72.

Weight gain associated with neuroleptic medication: a review.

Stanton JM.

Eating Disorders Service, Auckland Hospital, New Zealand.

In this article we review the empirical literature on weight gain associated with neuroleptic drug use. Weight gain, which appears to be associated with an increase in appetite, is variable but likely to be larger initially and then plateau. Clozapine and low-potency phenothiazines are associated with the largest gains and molindone with weight loss, but the mechanism is not known. Amantadine and fenfluramine may reverse weight gain to some degree. Dietary fat seems to play an important role in obesity, and research is needed to increase the data base and elucidate possible mechanisms. Studies are also needed to evaluate preventive strategies and to determine which drugs are least likely to produce weight gain as well as which drugs could be added to a neuroleptic regimen to control weight.

Publication Types:
   Review

PMID: 7481576 [PubMed - indexed for MEDLINE]

4: J Clin Psychiatry. 1993 Apr;54(4):160-1.

Molindone and weight loss.

Heikkinen H, Outakoski J, Meriläinen V, Tuomi A, Huttunen MO.

Publication Types:
   Clinical Trial
   Comparative Study
   Letter
   Randomized Controlled Trial

PMID: 8486596 [PubMed - indexed for MEDLINE]

5: J Clin Psychopharmacol. 1989 Aug;9(4):268-76.

Molindone hydrochloride: a review of laboratory and clinical findings.

Owen RR Jr, Cole JO.

Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, Maryland.

Molindone hydrochloride, a dihydroindolone neuroleptic, is structurally distinct from other classes of neuroleptics. Molindone exhibits many similarities to other neuroleptics, including dopamine receptor blockade, antipsychotic efficacy, and extrapyramidal side effects. Despite these similarities, molindone also has atypical properties and inhibits the enzyme monoamine oxidase in vitro and in
vivo. Several studies have shown that molindone causes less dopamine receptor supersensitivity than other neuroleptics and thus may be less likely to cause tardive dyskinesia. It also appears to have a greater effect on mesolimbic and mesocortical dopamine neurons than on those in the nigrostriatal dopamine system. Clinically, molindone has a tendency to cause weight loss and may have less effect on seizure threshold than conventional antipsychotic agents. The authors
review the laboratory and clinical data on molindone and discuss the relevance of atypical research findings to the clinical character-istics of this antipsychotic agent.

Publication Types:
   Review

PMID: 2671060 [PubMed - indexed for MEDLINE]

6: Am J Psychiatry. 1977 Mar;134(3):302-4.

Weight reduction in schizophrenics by molindone.

Gardos G, Cole JO.

The weight-reducing property of molindone, a recently introduced antipsychotic drug, was tested in 9 hospitalized chronic schizo-phrenic patients. There was an average weight loss of 7.6 kg after 3 months on molindone; most of the loss occurred during the first month. The mechanism producing this weight loss is uncertain, but a central anorexigenic effect may be an important factor.

PMID: 842709 [PubMed - indexed for MEDLINE]


Best regards . . .

Ivan
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