Mary A. Gutierrez

Venlafaxine: a 2003 update.

BACKGROUND venlafaxine has been available for use as an antidepressant in the United States for a decade. OBJECTIVE Comprehensive reviews of venlafaxine have been published elsewhere; thus, this update focuses on newer issues of treatment remission in depression, treatment-resistant depression, and extended-release venlafaxine for generalized anxiety disorder (GAD). METHODS Relevant clinical literature from 1993 through 2003 was identified from database searches of MEDLINE and International Pharmaceutical Abstracts, and from manual searches of reference lists of the identified papers. Search terms included venlafaxine extended-release, venlafaxine XR, treatment-resistant depression, depressive disorders, anxiety disorders, generalized anxiety disorder, and antidepressive agents second generation. RESULTS With its dual action of serotonin and noradrenergic reuptake inhibition, venlafaxine has been shown to be superior in efficacy to selective serotonin reuptake inhibitors for severe major depressive disorder, treatment-resistant depression, and depressive symptom remission. Its demonstrated efficacy for both short- and long-term treatment of GAD has led to its use for obsessive-compulsive disorder and chronic pain syndromes, although inadequate clinical literature currently exists to support these latter 2 uses. In the past decade, no new or unexpected adverse events have been identified with venlafaxine therapy, except a possibly greater risk of fatal overdose compared with other serotonergic drugs, suggesting the need for caution in patients with suicidal ideation. Because venlafaxine is a potent serotonin agonist, caution must also be exercised to prevent the possibility of serotonin syndrome when used with other serotonin agonists, and its dose should be tapered very gradually to minimize the risk of a serotonin withdrawal reaction. CONCLUSION Venlafaxine has emerged as a successful post-SSRI-era antidepressant with an expanded range of uses since it was first marketed.

Ziprasidone: An atypical antipsychotic drug for the treatment of schizophrenia

BACKGROUND Over the past decade, use of the atypical antipsychotic drugs clozapine, risperidone, olanzapine, and quetiapine has significantly changed the treatment of schizophrenia in the United States. The ability to make optimal drug choices will depend on determining whether there are clinically important differences between these drugs. OBJECTIVE This review describes ziprasidone, the most recently introduced antipsychotic drug. Its mechanism of action, pharmacokinetics, and adverse-effect profile are discussed, and the results of clinical efficacy trials are summarized. METHODS This review of ziprasidone is based on data from premarketing clinical efficacy and safety trials, a briefing document from the US Food and Drug Administration Psychopharmacological Drugs Advisory Committee, published studies, and abstracts presented at national and international meetings. International Pharmaceutical Abstracts and MEDLINE were searched for relevant citations, with no limitation on year. RESULTS Ziprasidone has been reported to be an effective antipsychotic drug for both positive and negative symptoms of schizophrenia, and long-term use has been effective in preventing relapse. Its 5-hydroxytryptamine (HT)1D-antagonist and 5-HT(1A)-agonist activity are consistent with a potential for antidepressant and anxiolytic activity beyond its antipsychotic effects. Ziprasidone has been associated with a low incidence of sedative effects, a low likelihood of extrapyramidal symptoms and postural hypotension, and no anticholinergic effect, although it may cause transient hyperprolactinemia. Unlike most atypical antipsychotic drugs, ziprasidone is not associated with weight gain, hyperlipidemia, or elevated plasma glucose levels. It is, however, more likely than other atypical antipsychotic drugs to increase the QTc interval (QT interval corrected for heart rate). For acute psychotic symptoms in patients with schizophrenia, schizoaffective disorder, or acute mania, ziprasidone is administered twice daily at a usual daily dose of 80 to 160 mg, whereas 40 mg/d may be an effective maintenance dose. CONCLUSIONS Differences in efficacy and tolerability between existing atypical antipsychotic drugs allow individualization of drug therapy for patients with schizophrenia or schizoaffective disorder. Ziprasidone differs from other atypical antipsychotic drugs in several clinically important ways, although further experience is necessary to clarify the significance of these differences.

Sexual dysfunction and psychotropic medications.

Psychotropic drugs are often associated with sexual dysfunction. The frequency of antidepressant-associated sexual dysfunction is greatly underestimated in clinical trials that rely on patient self-report of these adverse events. Direct inquiry reveals that delayed orgasm/ejaculation occurs in >50% and anorgasmia in at least one third of patients given selective serotonin reuptake inhibitors. Antidepressant-induced sexual dysfunction can be successfully managed. A different antidepressant without significant sexual effects, such as bupropion or mirtazapine, can often be substituted. Other strategies involve drug holidays or adjunctive therapy with drugs such as sildenafil. Dopamine antagonist antipsychotic drugs are most commonly associated with decreased libido. The newer atypical antipsychotics, with less effect on dopamine, are less commonly associated with sexual dysfunction. Sexual dysfunction is commonly reported with seizure disorders, and many anticonvulsant drugs affect levels of sex hormones. Because sexual dysfunction can be related to many factors, care must be taken to establish the patients baseline sexual functioning before the initiation of psychotropic drug therapy and to rule out other etiologies before drugs are implicated as causative.

Management of and Counseling for Psychotropic Drug‐Induced Sexual Dysfunction

Clinicians are increasingly faced with the need to identify, treat, and counsel patients regarding psychotropic drug‐induced sexual dysfunction. Antipsychotic and antidepressant drugs have both rational mechanisms to explain their effects on sexual function and established literature documenting these effects. The agents have potential for causing decreased libido, delayed ejaculation, and anorgasmia. Management and counseling can be highly effective for patients taking these agents.

Pharmacologic treatment strategies for sexual dysfunction in patients with epilepsy and depression.

Sexual dysfunction is a frequently encountered comorbid condition in patients with many medical and psychiatric conditions, such as epilepsy and depression. Most depressed patients experience some type of sexual dysfunction, decreased sexual desire being the most common. The association of sexual dysfunction with epilepsy is less clear. Changes in sex hormone levels are common in patients with epilepsy and may be attributable to the disease or to antiepileptic drugs (AEDs). Sexual dysfunction associated with depression or epilepsy is generally treated according to standard guidelines for the management of sexual disorders, since data from special populations are not available. The most common forms of female sexual dysfunction are lack of sexual desire and difficulty achieving orgasm. There are no approved pharmacotherapies for female hypoactive sexual desire disorder or female orgasmic disorder. Female sexual arousal disorder is treated with estrogen replacement therapy when indicated or vaginal lubricants. The most common male sexual dysfunction disorders are premature ejaculation and erectile dysfunction. Phosphodiesterase type-5 inhibitor drugs are now the first-line treatment for erectile dysfunction, and selective serotonin reuptake inhibitors and topical anesthetic creams are nonapproved but effective treatments for premature ejaculation. Testosterone and aromatase inhibitors have been used investigationally to treat sexual dysfunction in men taking AEDs. Patient education and follow-up appointments are essential to ensure optimal outcomes of pharmacologic treatments for sexual dysfunction.