A risk-benefit assessment of sulpiride in the treatment of schizophrenia.

Sulpiride is a substituted benzamide with a selective action on receptors of the dopamine D2-like family, and clinical and pharmacological data suggest that it could be considered to be an atypical antipsychotic. Sulpiride penetrates the blood-brain barrier poorly because of its low lipid solubility. It is mainly excreted unchanged in the urine, and accumulation of the drug could occur in patients with renal dysfunction and possibly in elderly patients with declining glomerular filtration rate. At low dosages (50 to 150 mg/day), sulpiride produces a disinhibiting and antidepressant effect, which is probably related to its action on D2 presynaptic autoreceptors, thus facilitating dopaminergic neurotransmission. Data have confirmed the efficacy of sulpiride in patients with acute or chronic schizophrenia during both short and long term treatment, but long term, placebo-controlled trials are still lacking. It is still doubtful whether sulpiride is more effective than typical antipsychotics for the treatment of negative symptoms. Data from clinical studies are controversial; the majority of authors indicate that sulpiride produces a better recovery rate from negative than from positive symptoms at low doses, but it shows a similar efficacy either on negative and positive symptoms at higher doses. The safety profile of sulpiride is similar to that of typical antipsychotics, although the frequency of adverse effects seems to be globally lower. Extrapyramidal reactions appear generally to be mild. Autonomic effects occur less frequently with sulpiride than with typical antipsychotics, showing no clinically relevant influence on cardiovascular parameters and, on the whole, good tolerability in elderly patients. Sulpiride is known to induce prolactin elevation in both serum and CSF, which may be associated with impotence in men and diminished gonadal function in women; these effects appear to be dosage-dependent. Sulpiride can be considered to be an atypical antipsychotic, considering its action on negative, defective symptoms, its partial activity against positive symptoms, and its low incidence of extrapyramidal adverse effects. Sulpiride could find its specific therapeutic role in elderly patients with schizophrenia, as it shows a good margin of safety between therapeutic dosages and toxic concentrations.

Depressive symptoms and schizophrenic relapses: the effect of four neuroleptic drugs.

1. A prevalence of depressive symptomatology, ranging from 25% to 80% has been reported during the course of schizophrenia. 2. Depressive symptoms were assessed in 144 schizophrenic patients (DSM IV) during an acute exacerbation phase. 3. Depressive symptoms showed a prevalence ranging from 5.5% (severe clinical pictures) to 54.8 (mild clinical pictures). 4. The authors did not find a correlation between depressive symptoms per se and the presence of negative psychotic symptoms. Depression may be linked not so much to negative symptoms but to the psychotic state itself. 5. Depressive symptomatology concurrently occurred with schizophrenic relapses and improved together with the psychotic clinical picture, independently of the neuroleptic drug employed. Haloperidol, haloperidol decanoate and fluphenazine decanoate all showed a similar improvement of depressive symptoms. 6. L-sulpiride showed a trend to be most effective on depressive symptomatology in comparison to the other neuroleptics.

Prediction of response to haloperidol in schizophrenia: neuroendocrine, neuromorphological and clinical variables.

Prediction of response to neuroleptics is a crucial topic since drug resistance phenomena can make the management of schizophrenia problematic and further deteriorate the outcome. Cerebral atrophy and enlarged ventricles have been suggested as the structural changes underlying negative symptoms and poor response to neuroleptic treatment. A higher percentage of non-suppressors to the dexamethasone suppression test (DST) among negative schizophrenics has been reported. Twenty-four schizophrenic in-patients, of both sexes, mean age 26.62 +/- 5.26 years, diagnosed according to DSM-III-R, with a mean duration of illness of 4.86 +/- 3.99 years, were treated with haloperidol 4-20 mg/day p.o. for 4 weeks. Clinical picture and extrapyramidal side effects were evaluated using BPRS and Simpson and Angus Scale at the beginning and end of the study. Ventricular brain ratio and basal and post-DST cortisol levels were evaluated at admission. The severity of the psychopathological picture, particularly positive symptoms at admission, were correlated to a higher amelioration at BPRS. Patients with ventricular enlargement and non-suppressors to DST showed higher variability of BPRS at baseline and more unpredictable clinical outcome than patients with normal ventricular brain ratio (VBR) and suppressors, even if a real difference in clinical outcome between patients characterized by normal or pathological parameters cannot be defined.

Long term efficacy of paroxetine in major depression: A study with plasma levels.

Depressive disorders can be regarded as recurrent and chronic conditions that may reduce the quality of life and work output of patients. Data on the long-term efficacy of paroxetine appear to indicate that it is an effective maintenance treatment. Our aim was to measure paroxetine concentrations in plasma in order to optimize its clinical efficacy and tolerability during long-term treatment. We studied 35 patients aged 23-70 years, suffering from Major Depressive Disorder (recurrent). These patients received 10-50 mg of paroxetine once a day for one year; they were evaluated at baseline, after 2 weeks and then after 1,2,6,9 and 12 months by BPRS, HRS-D and HRS-A rating scales, and at the same time, any side-effects were assessed and samples for paroxetine plasma determination were also collected. Results confirmed the efficacy and tolerability of paroxetine for long-term treatment. We observed a curvilinear relationship between plasma paroxetine levels and improvement on the HRS-D with greater clinical amelioration at plasma levels between 20 and 70 ng/ml.