Aripiprazole monotherapy in the treatment of acute bipolar I mania: a randomized, double-blind, placebo- and lithium-controlled study.

OBJECTIVES: To evaluate the efficacy and safety of aripiprazole as acute and maintenance of effect monotherapy for acute bipolar mania. METHODS: Patients with acute bipolar I mania (DSM-IV-TR: YMRS > or =20), manic or mixed (with or without psychotic features) were randomized to double-blind aripiprazole (15-30 mg/day; n=155), placebo (n=165) or lithium (900-1500 mg/day; n=160) (1:1:1) for 3 weeks. Aripiprazole- and lithium-treated patients remained on blinded treatment for 9 additional weeks. The primary outcome was the mean change from baseline in YMRS Total score (LOCF) to Week 3. Secondary outcomes included the mean change from baseline in YMRS Total score (LOCF) at all other timepoints up to Week 12. RESULTS: Aripiprazole demonstrated significantly greater improvement than placebo in mean YMRS Total score from baseline to Day 2 (-4.3 vs.-2.8; p=0.003), and up to Week 3 (-12.6 vs. -9.0; p<0.001). Significant improvement in YMRS Total score was also seen with lithium versus placebo at Week 3 (-12.0 vs. -9.0; p=0.005). Improvements in YMRS Total score were maintained to Week 12 for aripiprazole (-14.5) and lithium (-12.7). Response rates at Week 3 were significantly higher with aripiprazole (46.8%) and lithium (45.8%) than placebo (34.4%; both p<0.05, LOCF); increasing to Week 12 with aripiprazole (56.5%) and lithium (49.0%). Most common adverse events with aripiprazole were headache, nausea, akathisia, sedation, and constipation; with lithium were nausea, headache, constipation, and tremor. CONCLUSIONS: Aripiprazole provided statistically significant improvement of acute mania within 2 days, continuing over 3 weeks and sustained over 12 weeks. The magnitude of improvement to Week 12 was similar with aripiprazole and lithium.

Intramuscular aripiprazole or haloperidol and transition to oral therapy in patients with agitation associated with schizophrenia: sub-analysis of a double-blind study.

OBJECTIVE: A sub-population analysis of 325 patients with agitation (Positive and Negative Syndrome Scale Excited Component [PEC] score > or = 15 and < or = 32; score of > or = 4 on > or = 2 items) associated with schizophrenia in a randomized, double-blind study investigating the efficacy and tolerability of intramuscular (IM) aripiprazole 9.75 mg, IM haloperidol 6.5 mg, or IM placebo and the transition to oral therapy. RESEARCH DESIGN AND METHODS: Over 24 h, patients could receive up to three IM injections; the second and third administered > or = 2 and > or = 4 h, respectively, after the first, if deemed clinically necessary. Following IM treatment, oral aripiprazole or haloperidol was administered for 4 days. The primary efficacy measure was the mean change in PEC score from baseline at 2 h. RESULTS: At 2 h, mean improvements in PEC scores with IM aripiprazole (-8.0) were significantly greater versus IM placebo (-5.7; p < or = 0.01), and similar versus IM haloperidol (-8.3). Secondary efficacy measures also significantly improved with active IM treatment versus IM placebo. Continuation with oral treatment provided continued efficacy with both active treatments. The safety profiles of IM and oral aripiprazole were similar. The incidence of extrapyramidal symptom-related adverse events was 0% with IM aripiprazole, 1.6% with IM placebo and 16.5% with IM haloperidol. CONCLUSION: Intramuscular aripiprazole is effective in patients with acute agitation associated with schizophrenia, comparable to IM haloperidol, and enables convenient transfer to oral aripiprazole therapy.

Possible dihydroepiandrosterone-induced mania.

BACKGROUND: Dehydroepiandrosterone (DHEA) is among the most abundant steroids in the human body and appears to have diverse biochemical activities. This multifunctional hormone has long been a compound of interest to research psychiatrists. Its recent promotion and availability as an over-the-counter supplement to the general public has led to widespread use. Little is known about potential adverse effects of DHEA when consumed on an acute or chronic basis. We report a case of mania in an older man acutely admitted to our psychiatric facility with no previous personal or family history of bipolar disorder that appeared to be related to recent DHEA use. The patient had initiated DHEA use 6 months prior to admission and was taking 200-300 mg/day at the time of presentation. METHODS: He was treated with valproic acid 500 mg twice daily. RESULTS: The patient showed sufficient improvement to be discharged following a 7-day inpatient hospitalization. CONCLUSIONS: A wide range of medications have been associated with the induction of hypomania and mania, and we have provided a brief discussion of the potential for DHEA to trigger manic symptoms.

Ethical approach in contemporary psychiatry: a pragmatic approach in a psychiatry access center.

The field of mental health involves many ethical issues. As health care systems change to meet the demands of managed care it will be important to address these issues. At one academic center, a new service recently created to expand psychiatric care has been developed and implemented with ongoing attention to several common and important ethical concerns. A practical approach to the provision of mental health care services in light of issues such as confidentiality, informed consent, treatment refusal, commitment, and the suicidal patient is discussed.

Interactions between antipsychotic and antihypertensive drugs.

OBJECTIVE: To provide a comprehensive review of the pharmacokinetic and pharmacodynamic interactions between antipsychotics and antihypertensive and to provide recommendations for the selection of antihypertensive in patients receiving antipsychotic therapy. DATA SOURCES: A MEDLINE search of the English-language literature was used to identify pertinent human and animal studies, reviews, and case reports. STUDY SELECTION: All available sources were reviewed. DATA EXTRACTION: Background information was obtained from comprehensive reviews. Individual case reports were assimilated, and pertinent data were extracted. DATA SYNTHESIS: Because hypertension is common in patients with psychiatric illness and antihypertensive agents are used for a multiplicity of indications, significant numbers of patients receive concurrent therapy with antihypertensives and antipsychotics. Many antipsychotics may block the antihypertensive efficacy of guanethidine and related drugs. The interaction between clonidine and antipsychotics is defined less clearly. Limited data suggest possible additive hypotensive effects when chlorpromazine and methyldopa are given in combination. Increased plasma concentrations of thioridazine with a resultant increase in adverse effects have been reported when propranolol or pindolol are added to the regimen. A similar increase in chlorpromazine concentrations has been reported when propranolol was added. Although there are no reports documenting an interaction between a calcium-channel antagonist and an antipsychotic, the possible inhibition of oxidative metabolism of antipsychotics, additive calcium-blocking activity, and additive pharmacodynamic effects are theorized. Hypotension and postural syncope were reported in a patient given therapeutic dosages of chlorpromazine and captopril, and in 2 patients when clozapine was added to enalapril therapy. CONCLUSIONS: No antipsychotic-antihypertensive combination is absolutely contraindicated, but no combination should be considered to be completely without risk. Antihypertensives with no centrally acting activity, such as diuretics, may be the least likely to result in adverse reactions. The combination of the beta-antagonists propranolol or pindolol with thioridazine or chlorpromazine should be avoided if possible. Scrupulous patient monitoring for attenuated or enhanced activity of either agent is essential whenever antipsychotics and antihypertensives are given concurrently.

Mood congruent and incongruent psychotic depressions: are they the same?

DSM-III and DSM-III-R instruct the clinician, if possible, to classify major depression with psychotic features into either the mood congruent (MC) or mood incongruent (MI) subtype. Patients hospitalized on a psychiatric unit for major depression with psychotic features were classified as predominantly MC or MI. The MC and MI groups did not differ significantly on a number of demographic or symptom severity variables. Thirteen (50%) MI patients experienced at least one MC symptom and 10 (71%) MC patients experienced at least one MI symptom. Overall, 25 (58%) of these patients experienced both MC and MI symptoms. This study demonstrates that subtyping psychotic depression into MC and MI subtypes is seldom an 'either-or' decision. Indeed, these results combined with findings from previous research suggests that there is no compelling scientific evidence for subclassifying psychotic depression into subtypes.

Emotionality changes in rats following chronic exercise.

The effect of chronic endurance exercise on the emotionality of male albino rats was studied in five experimental groups: Controls, Runners, Walkers, Swimmers and Waders. Runners and Swimmers were trained for 8 weeks using programs which produced significant bradycardia and cardiac hypertrophy. Walkers and Waders received comparable handling and exposure to the psychological aspects of the treadmill running and swimming routines but were not physically trained. The Control group was allowed only home cage activity. After 8 weeks all animals were tested for their level of emotionality using the tunnel emergence test and the open field test. The emergence test was judged to be too stressful for the Sasco rat strain used in this study since many rats failed to emerge in one hour. Three measurements in the open field: urination, defecation and central squares also lacked power to discriminate emotionality because of their very low level of occurrence. The Control rats had significantly longer latency times, which indicates that the additional handling received by the other groups reduced their emotionality. The significantly larger number of total squares entered by the Runners and Swimmers supports the hypothesis that chronic physical exercise does function to lower emotionality in the rat.