A naturalistic multicenter study of intramuscular olanzapine in the treatment of acutely agitated manic or schizophrenic patients.

BACKGROUND: We conducted a naturalistic, multicenter, 24-hour, nonrandomized, observational study describing for the first time the effectiveness and safety of intramuscular (IM) olanzapine to control agitation and aggression in "real world" patients with psychosis. The data thus obtained was compared with that reported from randomized double-blind clinical trials. METHOD: 92 patients attending psychiatric emergency settings were enrolled. The study subjects were 44 male and 48 female patients with a mean age of 36.5+/-12 years and DSM-IV-TR diagnoses of schizophrenia (48.9%), psychotic disorder not specified (23.9%) or bipolar disorder (27.2%). 10 mg IM olanzapine was administered to all patients. An optional second injection was permitted> or =2 hours later in line with hospital policy. Evaluations (PANSS-EC and CGI-S) were performed at baseline and 2 and 24 hours following the IM injection. RESULTS: Two hours after IM olanzapine was administered, a mean decrease of -9.6 in the PANSS-EC from a baseline score of 26.5 was recorded. At the 24-hour endpoint a statistically and clinically significant reduction in the PANSS-EC scores (11.6+/-5.3) was observed as compared with values at study entry (26.5+/-5.9) and at 2 hours endpoint (16.9+/-9.3), which represent a mean decrease of -14.9 and -5.3, respectively. CONCLUSION: The present naturalistic study provides naturalistic data on the effectiveness of IM olanzapine in the treatment of acute agitation in patients with schizophrenia or bipolar mania that is in line the data obtained in randomized double-blind clinical trials.

Antidepressant combinations: epidemiological considerations.

OBJECTIVE: To evaluate the treatment options in patients who do not respond appropriately to a single antidepressant alone. METHOD: The medical literature was reviewed. RESULTS: A number of strategies are available if a patient fails to respond adequately to initial antidepressant treatment, including the combination with another psychoactive drug. Evidence published to date appears to suggest that benzodiazepines are the drugs most frequently combined with antidepressants. The combination of two antidepressants together is less common, occurring in approximately 5-15% of cases showing a poor initial response. The key figures involved in such co-prescription are psychiatrists. CONCLUSION: There appears to be considerable variability in the data concerning combined prescription of antidepressants, with differences arising depending on the type of physician, the type of patient or illness and the geographical area. It is also unclear how closely research findings parallel with what doctors do in everyday practice.

Neuropharmacological basis of combining antidepressants.

OBJECTIVE: To review the neuropharmacological basis of antidepressant combination therapy. METHOD: Literature searches and other relevant material were obtained and reviewed. RESULTS: The overall clinical aim of combining antidepressants is to increase the efficacy whilst minimizing the side effects. Although such prescriptions are frequently based on the previous experience and knowledge, a sound neuropharmacological basis to support these combinations is desirable. When combining antidepressants, it is important to combine mechanisms of action, rather than simply one drug with another, and to aim for synergistic effects. The possibilities of combining mechanisms of action should also be exploited to the full if necessary, and the potential exists for combining two independent actions that have synergistic effects on the serotonergic, noradrenergic and even the dopaminergic systems. CONCLUSION: Unfortunately, there are still, as yet, insufficient data to categorically justify choosing one or other combination based only on the neuropharmacological evidence.

Combined antidepressants: clinical experience.

OBJECTIVE: To review the current literature on the use of combinations of antidepressive agents. METHOD: Literature searches were undertaken and reviewed on the use of combinations of antidepressants. RESULTS: Data sources included surveys, analyses of prescription records, decision algorithms, clinical reports, and studies comparing the monotherapy with combination therapy. More recent surveys recommend combining different selective serotonin reuptake inhibitors (SSRIs), an SSRI plus bupropion or dual action antidepressants plus an SSRI. Decision algorithms recommend an SSRI plus tricyclic antidepressant (TCA) and more recently bupropion plus venlafaxine or mirtazapine. Few controlled clinical trials comparing the combined therapy with monotherapy have been conducted. Beneficial effects have been reported with combinations of TCAs plus mianserin or SSRIs plus mirtazapine. CONCLUSION: Adding or combining antidepressant medications has advantages for the speed of onset and maintaining the existing response. More rigorous clinical trials comparing combination therapy with monotherapy and for the development of rational treatment guidelines are required.

Potentiation strategies for treatment-resistant depression.

OBJECTIVE: To review the pharmacological basis of antidepressant potentiation in combination therapy and the clinical evidence for its efficacy. METHOD: Literature searches were undertaken and the results reviewed. RESULTS: Treatment-resistant depression is common (15-30%). Various strategies exist for dealing with resistant depression, including pharmacological potentiation, i.e. adding a treatment that itself does not have antidepressant actions but that enhances the efficacy of the original treatment. Lithium, triiodothyronine (T3) and buspirone are the best studied potentiating drugs, although other options include pindolol, dopaminergic agents, second-generation antipsychotics, psychostimulants, hormones and anticonvulsants. CONCLUSION: Several pharmacological potentiation strategies exist. Whilst good evidence exists for lithium combined with antidepressants, although good results have also been reported with augmentation strategies involving T3 or buspirone.

Use of antidepressant combinations: which, when and why? Results of a Spanish survey.

OBJECTIVE: The present study uses the data from a large survey conducted to examine the general practice of Spanish psychiatrists on the use of antidepressant combinations in the treatment of depressive disorders. METHOD: The sample was drawn from specialists and psychiatric residents practicing in Spain who were respondents to a questionnaire distributed during an annual national psychiatry meeting and sent by mail. RESULTS: A total of 1032 questionnaires were collected; following the data-filtering, 831 were analysed. Most psychiatrists (89%) believe that many patients do not respond to the first treatment; in such cases of non-response, 58% choose a combination of antidepressants as the next treatment option. Reasons for using the combined treatments include greater efficacy (57%), overcoming resistance to the first antidepressant (27%), faster onset of action (21%) and avoidance of side effects (17%). The most sought after pharmacological profile was serotonergic-noradrenergic (96%) and the most popular combinations were selective serotonin reuptake inhibitor (SSRI) + mirtazapine, SSRI + reboxetine and SSRI + tricyclic antidepressant. CONCLUSION: Antidepressant combinations are frequently used in clinical practice. Pharmacological profiles are always considered and SSRIs + mirtazapine is the option usually chosen.

[Once weekly fluoxetine, tolerability and safety according to use patterns in the psychiatric clinical practice]. / Fluoxetina semanal. Tolerabilidad y seguridad según patrones de uso en la práctica clínica psiquiátrica.

INTRODUCTION: Treatment with selective serotonin reuptake inhibitors (SSRI) has become generalized in all the medical setting although its efficacy and good tolerability may be affected by long term non-compliance. Once weekly fluoxetine could improve compliance due to the comfort of its use. The objective is to evaluate the safety, tolerability and efficacy of once weekly fluoxetine (90 mg) in a sample of out-patients, following naturalistic criteria in the usual clinical practice. METHOD: A total of 46 patients (age: 41.89 +/- 1.85) who received once weekly fluoxetine for at least 3 months (mean time: 135.24 days) were analyzed retrospectively. Clinical Global Impression of Severity (CGI-S) at the onset and end of the period evaluated, presence of adverse events, drop-out index and impression of patient's satisfaction with the treatment and use pattern were used. RESULTS: The mean of the final CGI-S was 2.09, compared with the onset 3.09 (p < 0.02), indicating significant improvement in the efficacy with once weekly fluoxetine. The most frequent adverse effects were: anxiety (10.87 %), headache (8.69 %) and restlessness (8.69 %) related with once weekly fluoxetine. Compliance was very high at the onset (99 %) and at the end (96 %). Ten patients dropped-out of the treatment (27.74 %), 6 due to appearance of undesirable effects (anxiety, headache and insomnia), three due to voluntary wish and only one due to lack of efficacy. The CGI of satisfaction of clinical global efficacy on the final visit was 1.43 (satisfied-very satisfied) and the CGI of satisfaction for the treatment pattern was 1.17 (very satisfied). CONCLUSION: Change to once weekly fluoxetine generally improves satisfaction of treatment efficacy and its use pattern, although some patients return to the initial regime after adverse effects appear.

Fluoxetine in the prevention of depressive recurrences: a double-blind study.

Optimal outcomes from depression treatment are long-term recovery and, in the case of recurrent depression, prevention of new episodes. However, few data are available concerning the long-term efficacy of antidepressants in prophylactic treatment to prevent recurrences of depression. The efficacy and safety of fluoxetine 20 mg/day was evaluated in reducing the number of depressive episodes and in extending the time free of symptoms in patients with recurrent unipolar major depression. Patients with recurrent unipolar major depression according to DSM-III-R criteria and who responded to 32 weeks of open-label fluoxetine were randomly assigned to receive fluoxetine 20 mg/day (N = 70) or placebo (N = 70) for 48 weeks of double-blind maintenance treatment. Outcome measures were the percentage of recurrences and time to recurrence. Safety assessments included treatment-emergent adverse events, reasons for discontinuation, vital signs, and laboratory measures. Fluoxetine was associated with a statistically significantly smaller percentage of patients who had a recurrence compared with placebo (20% vs. 40%; chi2 analysis, p = 0.010). The symptom-free period was significantly longer for patients treated with fluoxetine versus placebo (295 vs. 192 days; Kaplan-Meier estimates, log-rank test, p = 0.002). Treatments were well tolerated during maintenance treatment. The only statistically significant difference in adverse events between treatment groups was anxiety, which was more frequent in the placebo group (fluoxetine, 12.9% vs. placebo, 30%; chi2 analysis, p = 0.013). Two placebo-treated patients and no fluoxetine-treated patients were withdrawn because of adverse events. In conclusion, fluoxetine at 20 mg/day was effective and well tolerated for the prophylactic treatment of recurrent unipolar major depression.

SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients.

The authors analyzed the incidence of sexual dysfunction (SD) with different selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, paroxetine, and sertraline) and hence the qualitative and quantitative changes in SD throughout time in a prospective and multicenter study. Outpatients (192 women and 152 men; age = 39.6 +/- 11.4 years) under treatment with SSRIs were interviewed with an SD questionnaire designed for this purpose by the authors and that included questions about the following: decreased libido, delayed orgasm or anorgasmia, delayed ejaculation, inability to ejaculate, impotence, and general sexual satisfaction. Patients with the following criteria were included: normal sexual function before SSRI intake, exclusive treatment with SSRIs or treatment associated with benzodiazepines, previous heterosexual or self-erotic current sexual practices. Excluded were patients with previous sexual dysfunction, association of SSRIs with neuroleptics, recent hormone intake, and significant medical illnesses. There was a significant increase in the incidence of SD when physicians asked the patients direct questions (58%) versus when SD was spontaneously reported (14%). There were some significant differences among different SSRIs: paroxetine provoked more delay of orgasm or ejaculation and more impotence than fluvoxamine, fluoxetine and sertraline (chi 2, p < .05). Only 24.5% of the patients had a good tolerance of their sexual dysfunction. Twelve male patients who suffered from premature ejaculation before the treatment preferred to maintain delayed ejaculation, and their sexual satisfaction, and that of their partners, clearly improved. Sexual dysfunction was positively correlated with dose. Patients experienced substantial improvement in sexual function when the dose was diminished or the drug was withdrawn. Men showed more incidence of sexual dysfunction than women, but women's sexual dysfunction was more intense than men's. In only 5.8% of patients, the dysfunction disappeared completely within 6 months, but 81.4% showed no improvement at all by the end of this period. Twelve of 15 patients experienced total improvement when the treatment was changed to moclobemide (450-600 mg/day), and 3 of 5 patients improved when treatment was changed to amineptine (200 mg/day).

[Sexual dysfunction secondary to SSRIs. A comparative analysis in 308 patients]. / Disfunción sexual secundaria a ISRS. Análisis comparativo en 308 pacientes.

UNLABELLED: The authors analyze the incidence of sexual dysfunction (SD) with different SSRIs (Fluoxetine, Fluvoxamine, Paroxetine and Sertraline) and hence the qualitative and quantitative changes in SD throughout time 308 outpatients (169 women, 139 men; mean +/- SD age = 41 +/- 7) under treatment with SSRIs were interviewed with an SD questionnaire designed for this purpose by the authors including questions about the following items decreased libido, delayed orgasm or anorgasmia, delayed ejaculation inability to ejaculation, impotence and general sexual satisfaction. Patients with the following criteria were included: normal sexual function before SSRIs intake, exclusive treatment with SSRIs or associated with benzodiazepines, previous heterosexual or self-orone current sexual practices. We excluded patients with previous sexual dysfunction, association of SSRIs with neuroleptics, recently hormone intake and significant medical illnesses. RESULTS: There is a significant increase in the incidence of SD when the physicians ask the patients direct questions (55.29%) versus spontaneous SD reported (14.2%). There are some significant differences among different SSRIs paroxetine provoked more delay of orgasm/ejaculation and more impotence than fluvoxamine, fluoxetine and sertraline (Chi square p < 0.05). Only 22.6% of the patients had a good tolerance about their sexual dysfunction. SD has positive correlation with the dose. The patients experienced substantial improvement in sexual function when the dose was diminished or the drug was withdrawn. Men showed more incidence of sexual dysfunction than women but women's sexual dysfunction was more intense than men. Seven of nine patients (77.7%) experienced total improvement when the treatment was changed to Moclobemide (450 mg/day) and two of four patients (50%) improved when treatment was changed to Amineptine.