Physostigmine and lithium response in the schizophrenias.

Conflicting reports concerning cholinomimetic-induced reduction of schizophrenic symptoms prompted the authors to study such changes in schizophrenic symptoms following physostigmine infusions in subgroups of patients with schizophrenic-like illness. These subgroups were defined by the presence or absence of antipsychotic response during a 2-week trial of lithium alone after physostigmine infusion. Patients who showed significant but temporary improvement in their thinking disturbance on serial Brief Psychiatric Rating Scale scores following physostigmine infusion subsequently responded to lithium; patients who failed to improve following physostigmine also failed to respond to lithium. The authors suggest that some schizophrenic-like illnesses may be biologically similar to mania both with respect to physostigmine and lithium-induced changes in symptomatology.

Therapeutic effects of pindolol on behavioral disturbances associated with organic brain disease: a double-blind study.

A double-blind, placebo-controlled crossover study was conducted to examine the effects of pindolol for the treatment of 11 patients with impulsive, explosive behaviors and other emotional-behavioral abnormalities as a consequence of brain disease or injury. Pindolol treatment was associated with significant therapeutic benefits without sedation and without the use-limiting side effects that occur with propranolol.

Fluphenazine plasma levels and clinical response.

Plasma levels of fluphenazine and clinical response were examined in 19 inpatient schizophrenics (DSM-III diagnoses) using a constant dose, steady-state methodology. A significant curvilinear correlation was demonstrated between clinical response and steady-state plasma levels of fluphenazine (p less than .05). A therapeutic range of plasma fluphenazine is suggested in the range of .13-.70 ng/ml. The lowest plasma level detected (.13 ng/ml) appeared to be well within the therapeutic range. The 9 patients with plasma fluphenazine levels in this range demonstrated a mean clinical improvement of 59% compared to 34% for patients with plasma levels above .70 ng/ml (p less than .01).

A comparison of differential white blood cell counts using manual technic and the Coulter S-Plus IV.

The results of 100-cell and 500-cell manual differential white blood cell counts were compared with those obtained using a Coulter S-Plus IV electronic particle counter. Significant (P less than 0.001) correlations were observed between the manual and instrument-derived data for percentages of granulocytes and lymphocytes.

Clinical response and plasma haloperidol levels in schizophrenia.

Plasma haloperidol levels were compared to clinical response during the first 14 days of drug treatment in 14 DSM III-diagnosed inpatient schizophrenic patients using an improved methodology, which utilized predetermined constant dosages and derived a therapeutic range of plasma haloperidol levels from a curvilinear regression analysis. An inverted U-shaped relationship was found which reflected a significant curvilinear correlation (r = 0.66, P less than 0.02) between plasma levels (as assayed by gas chromatography) and improvement on the Serial New Haven Schizophrenia Index. A therapeutic window was suggested by the present study, with optimum patient response associated with plasma haloperidol levels of 4.2-11.0 ng/ml for the first 2 weeks of treatment.

Adrenergic-receptor desensitization and course of clinical improvement with desipramine treatment.

alpha 2-Adrenergic receptor sensitivity was assessed during desipramine treatment by carefully monitoring clonidine-induced blood pressure changes, as well as symptomatology, in three patients with major depressive disorder. The data appear to be consistent with the hypothesis that the antidepressant action of desipramine is mediated by alpha 2-autoreceptor desensitization.

Schizophrenia and reduced cyclic AMP production: evidence for the role of receptor-linked events.

Reduced cyclic AMP (cAMP) production has been found in platelets of schizophrenic patients. cAMP is generated physiologically as a result of a series of steps beginning with receptor activation by a ligand, progressing through activation of the enzyme protein, adenylate cyclase. The deficit of cAMP found in the schizophrenic population may occur at any one, or at multiple steps in this cascade. The present study attempts to discriminate whether impaired adenylate cyclase itself was responsible for the cAMP deficit or whether abnormalities in receptor events or linkage are present in schizophrenics. The production of cAMP following direct stimulation of adenylate cyclase by NaF was contrasted with receptor mediated activation of adenylate cyclase by prostaglandin E1 (PGE1) in disrupted platelet preparations from schizophrenics and normal controls. cAMP formation stimulated by NaF was not different in platelets of schizophrenics as compared to controls, however, platelets of schizophrenics showed reduced response to PGE1 stimulation. The authors interpret these findings as evidence for a membrane associated abnormality of either receptor or receptor-adenylate cyclase linkage in the schizophrenias.

Plasma propranolol levels and their effect on plasma thioridazine and haloperidol concentrations.

The relationship between chronic oral dosage with a long-acting formulation of propranolol and plasma propranolol levels 22 to 23 hours later is described in 12 adult male patients with organic brain disease. Separately, the effects on plasma levels of thioridazine plus metabolites with concomitant rising dose long-acting propranolol administration were studied in five patients. Significant dose-related increases in levels of thioridazine and metabolites were found when long-acting propranolol was given. No changes in haloperidol levels were found in three patients studied in a similar protocol.

Propranolol treatment of assaultive patients with organic brain disease. A double-blind crossover, placebo-controlled study.

A double-blind, placebo-controlled crossover study was conducted to examine the effects of long-acting propranolol in the treatment of violent behavior associated with organic brain disease in 10 patients whose symptoms had proved refractory to various conventional medications. Long-acting propranolol treatment was associated with reductions of assaultive behavior without apparent sedative effects. Cautions are noted regarding potential undesirable side effects which may necessitate careful patient monitoring during treatment.

Haloperidol plasma and red blood cell levels and clinical antipsychotic response.

Two investigators have recently suggested therapeutic ranges for plasma haloperidol in the treatment of schizophrenia. An apparent optimal therapeutic range of red blood cell haloperidol as early as day 7 of the drug trial is described in this article. With continued treatment, an optimal plasma haloperidol range for response could be observed by day 14 of treatment. The previously described correlation between response at day 7 and plasma/red blood cell haloperidol ratio was confirmed but was found not to predict response at day 14 of drug treatment in this cohort of DSM-III schizophrenic patients.

Clinical relevance of thiothixene plasma levels.

The authors examined plasma levels of thiothixene and clinical response in 19 DSM-III diagnosed inpatient schizophrenics, using an improved methodology. A significant curvilinear correlation was demonstrated between clinical response and plasma levels for thiothixene (p less than 0.02). Optimal clinical response to thiothixene appears to be associated with plasma levels from 2.0 to 15.0 ng/ml (p less than 0.05). These findings suggest that laboratory measurement of thiothixene levels may assist in determining the minimum effective dose for individual patients.