Evidence-based pharmacologic treatment for people with severe mental illness: a focus on guidelines and algorithms.

Medication treatment of severe mental illness has been advanced and complicated by the introduction of numerous therapeutic agents. Practice guidelines based on research evidence have been developed to help clinicians make complex decisions. Studies of usual care suggest an important potential role for guidelines in improving the quality of medication treatment for people with severe mental illness. The authors review current evidence-based guidelines for medication treatment of persons with severe mental illness. Four categories of guidelines are described: recommendations, comprehensive treatment options, medication algorithms, and expert consensus. The authors note that more research is needed on optimal next-step strategies and the treatment of patients with comorbidity and other complicating problems. They discuss barriers to the implementation of guidelines, and they observe that the potential of guidelines and algorithms to promote evidence-based medication treatment for persons with severe mental illness depends on refinement of tools, progress in research, and cooperation of physicians, nonphysician clinicians, administrators, and consumers and family members.

Idazoxan, an alpha 2 antagonist, augments fluphenazine in schizophrenic patients: a pilot study.

Idazoxan, a selective alpha 2-adrenergic antagonist, was added to stable doses of fluphenazine treatment in six patients with schizophrenia who participated in a double-blind, placebo-controlled pharmacologic study. Compared with fluphenazine alone, combining idazoxan (mean dose, 120 mg/day) with fluphenazine (mean dose, 28 mg/day) resulted in a significant decrease in Brief Psychiatric Rating Scale total symptoms (p < 0.05). Symptom ratings returned to baseline upon idazoxan discontinuation. No significant effects of idazoxan were observed on fluphenazine levels in plasma or on extrapyramidal symptoms. These pilot data are compatible with the notion that increased noradrenergic neurotransmission may enhance the therapeutic effects of typical neuroleptics in schizophrenia.

The effect of prenatal treatment with MPTP or MPP+ on the development of dopamine-mediated behaviors in rats.

Systemic exposure to the neurotoxin MPTP produces a Parkinsonian syndrome in man and primates, but not in adult rats. However, embryonic rat dopamine neurons in cell cultures are selectively destroyed by MPTP. This study examined whether similar effects on dopamine neurons occur in vivo, by studying dopamine-mediated behaviors in rats prenatally treated with MPTP or its active metabolite MPP+. Pregnant rats were injected daily with MPTP, MPP+, or vehicle from gestational day (E)13 until birth. There were time-dependent increases in spontaneous locomotor and rearing activity. Offspring of both the MPTP and MPP+ groups were hyporesponsive to d-amphetamine (1 mg/kg IP) at postnatal day 21. This hyporesponsiveness persisted at postnatal day 50 in the pups from MPTP-treated mothers. However, the striatal concentration of dopamine and its metabolites DOPAC and HVA were not significantly affected by the prenatal MPTP or MPP+ treatments. Both MPTP and MPP+ groups had significantly increased stereotypic responses to apomorphine (0.2 mg/kg SC) on both postnatal days 21 and 50. These results demonstrated persistent postsynaptic supersensitivity to dopaminergic agonists following prenatal MPTP/MPP+ treatment. That fetal rats develop long-term sequelae after prenatal exposure to MPTP/MPP+ suggests a different sensitivity of the immature rat dopamine neurons than in adult rats. Understanding this difference may provide useful information in the development of animal models of Parkinson's Disease.

Moire interferometry near the theoretical limit.

The theoretical upper limit of moire interferometry is approached as the reference grating pitch approaches lambda/2 and its frequency approaches 2/lambda. This work demonstrates the method at 97.6% of the theoretical limit. A virtual reference grating of 4000 lines/mm (101,600 lines/in.) was used in conjunction with a phase type reflection grating of half of that frequency on the specimen. Sensitivity was 0.25 microm/fringe (9.8 microin./fringe). In-plane displacement fringes of excellent definition were obtained throughout the 76 x 51-mm (3 x 2-in.) field of view. They were very closely packed, exhibiting a maximum fringe density of 24 fringes/mm (610 fringes/in.). Effectiveness of moire interferometry near the theoretical limit was proved.