Martin L. Korn, MD Disclosures

A number of interesting presentations and new research studies were presented at the XII World Congress of Psychiatry in Yokohama, Japan. Cognitive behavior therapy (CBT) has been widely used in the treatment of depression and anxiety disorders. There is increasing evidence that some of the techniques may be used in the treatment of bipolar disorder and schizophrenia.[1] Turkington and associates[2] reported on a study using psychiatric nurses to apply these techniques to outpatients with schizophrenia. A total of 257 patients were administered 6 sessions of CBT over the course of 6 months. The results were compared with 165 patients treated with treatment as usual. Patients administered CBT demonstrated increases in insight, as well as decreases in overall symptomatology scores and burden of care measures. Depression decreased significantly as well. The effect at 9 months showed a significant improvement in insight, negative symptoms, and career involvement. This study therefore gave evidence that brief CBT interventions could be delivered in a cost-effective manner by psychiatric nurses.

Depot Antipsychotics
Long-acting typical injectable medications have been shown to increase compliance rates and thereby decrease rates of hospitalization.[3] Atypical neuroleptics have also been shown to be more clinically effective in decreasing rates of rehospitalization. For example, in a study by Rabinowitz and colleagues,[4] the percent of patients remaining in the community for 24 months was 52% for patients on typical neuroleptics, 67% who were treated with risperidone, and 69% treated with olanzapine. Yet, the lack of availability of a long-acting atypical neuroleptic has forced clinicians to choose between typical depot medications with a generally higher side effect burden and atypical oral neuroleptics. Long-acting injectable risperidone has recently been developed, which should help to resolve this clinical dilemma. In a study by Remington and colleagues,[5] patients with schizophrenia or schizoaffective disorder were administered 25 or 50 mg of long-acting risperidone every 2 weeks in an open-label study. A total of 397 patients were included in the study. Partial hospitalization rates decreased from 7% prior to the study to 3% at the end of the study. Outpatient visits also decreased significantly. Thus, long-acting injectable atypical neuroleptics will be a significant addition to the pharmacopoeia in the treatment of chronic psychotic conditions.

Sexual Dysfunction in Schizophrenia
Sexual dysfunction is increasingly being recognized as a problem among patients with a variety of psychiatric disorders. The difficulty has been widely recognized among patients with affective syndromes, in part due to antidepressant-induced dysfunction. In individuals with psychotic disorders, however, this problem has not received equal clinical attention. Dossenbach and colleagues[6] conducted a study that was a prospective observational study of health outcomes associated with antipsychotic medications in patients with schizophrenia. All care was at the discretion of the treating psychiatrist. Patients were followed for a period of 3 years. Patients were drawn from Latin America (35%), Africa and the Middle East (19%), Asia (17%), and Central and Eastern Europe (29%). The patients enrolled in the study were moderately ill. The overall presence of sexual dysfunction was 51%. Patients from Central and Eastern Europe reported the highest levels of overall sexual dysfunction (60%). The most severe cases of sexual dysfunction were reported in Europe and Latin America. Patients in Asia reported the lowest frequency and severity of dysfunction. The overall sexual dysfunction rate in Asia was 32%. The most common symptoms overall were loss of libido and impotence. There was also a significant level of galactorrhea in all patients and amenorrhea. Physicians underestimated the level of sexual dysfunction significantly.

Switching Neuroleptics During Treatment
The reasons why clinicians use a particular medication or class of medication is important to understand to evaluate the quality and nature of the decision-making process. This is particularly important with the newer but more costly atypical neuroleptic medications. A study in Germany assessed the prescribing procedures of 495 psychiatrists in private practice via questionnaire.[7] The reasons why physicians elected to continue or switch patients with schizophrenia to olanzapine were evaluated. The most important reasons that clinicians utilized olanzapine were perceived efficacy of the drug, improved side effect profile and tolerability factors, lack of full efficacy of previous treatments, type of psychopathology, and severity of illness. Although the cost of the medication was seen as a problem, this did not influence the clinical decision-making process.

Galantamine in Schizophrenia
Two interesting studies used galantamine in patients with schizophrenia. J.P. McEvoy[8] investigated the impact of using galantamine to improve smoking behavior. Preliminary findings with galantamine therapy have shown improvement in episodes of agitation in 1 patient (8 mg twice a day) and improved social and hygiene manners in another (12 mg twice a day). The author concluded that there is hope in establishing a therapeutic use for galantamine in patients with refractory schizophrenia.

A second study by Zhao and colleagues[9] described that patients with schizophrenia suffer from significant cognitive deficits. Atypical antipsychotic medications tend to improve these deficits compared with typical agents. Nevertheless, cognitive difficulties still remain a problem, even with the newer agents. Furthermore, the rate of cigarette smoking among patients with schizophrenia is much higher than the general population, leading to speculation about the role of nicotinic receptors in psychotic disorders.

Galantamine is a reversible cholinesterase inhibitor approved for use in Alzheimer's Disease.[10] The drug also acts at the nicotinic acetylcholine receptors.[11] This nicotinic receptor action may relate to the central cholinergic effects of the drug. McEvoy and colleagues reported on preliminary results of a study examining the effect of galantamine as a risperidone-augmenting agent in patients with schizophrenia. All patients were on a stable dose of 1-8 mg of risperidone for at least 7 days. Patients received 16, 24, or 32 mg of galantamine or placebo over the 28-day course of the study. There appeared to be some beneficial cognitive effects of this medication, particularly on omission errors on the Conners Continuous Performance Test. Because of the large variation in smoking rates, no definitive conclusions could be drawn about the effect of galantamine on smoking.

*In this activity, the author may discuss investigational products or unlabeled uses of FDA approved products.

References
Kingdon DG, Turkington D. The use of cognitive behavior therapy with a normalizing rationale in schizophrenia. Preliminary report. J Nerv Ment Dis. 1991;179:207-211.
Turkington D, Kingdon D, Turner T. Brief cognitive behavioural therapy for schizophrenia. Program and abstracts of the XII World Congress of Psychiatry; August 24-29, 2002; Yokohama, Japan. Abstract PO-74-3.
Youssef HA. Duration of neuroleptic treatment and relapse rate: a 5-year follow-up study with haloperidol decanoate. Clin Neuropharmacol. 1991;14(suppl 2):S16-21; discussion S22-23.
Rabinowitz J, Lichtenberg P, Kaplan Z, Mark M, Nahon D, Davidson M. Rehospitalization rates of chronically ill schizophrenic patients discharged on a regimen of risperidone, olanzapine, or conventional antipsychotics. Am J Psychiatry. 2001;158:266-269.
Remington G, Duchesne I, Devos E, et al. Long-acting risperidone: healthcare resource use. Program and abstracts of the XII World Congress of Psychiatry; August 24-29, 2002; Yokohama, Japan. Abstract PO-73-25.
Dossenbach M, Brunner M, Becker S, et al. Sexual dysfunction during treatment of schizophrenia: a largely underestimated problem. Baseline results from the 3-year Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study. Program and abstracts of the XII World Congress of Psychiatry; August 24-29, 2002; Yokohama, Japan. Abstract PO-73-41.
Linden M, Czekalla J, Holstein W, et al. Medical decision making when switching neuroleptic treatment in schizophrenic patients to olanzapine. Program and abstracts of the XII World Congress of Psychiatry; August 24-29, 2002; Yokohama, Japan. Abstract PO-73-47.
McEvoy JP. Galantamine's effect on smoking in schizophrenics. Program and abstracts of the XII World Congress of Psychiatry; August 24-29, 2002; Yokohama, Japan. Abstract PO-74-10.
Zhao Q, Huang F, James R. Pharmacokinetics of galantamine and risperidone. Program and abstracts of the XII World Congress of Psychiatry; August 24-29, 2002; Yokohama, Japan. Abstract PO-46-26.
Bonner LT, Peskind ER. Pharmacologic treatments of dementia. Med Clin North Am. 2002;86:657-674.
Lilienfeld S. Galantamine - a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS Drug Rev. 2002;8:159-176.