dihydrotachysterol and Schizophrenia

In this double-blind study dihydrotachysterol (DHT) was given orally to eight psychotic patients; in each case marked increases in psychosis and agitation accompanied increases in serum calcium and phosphorus within two weeks after active drug was substituted for placebo. In the three patients whose psychoses exhibited periodic spontaneous exacerbations, the agitated episodes grew more severe. Serum creatine phosphokinase (CPK) increased in all but one patient. By contrast, when three periodically psychotic patients received synthetic salmon calcitonin (SCT), the severity and frequency of agitated episodes decreased while CSF calcium increased in all three. These data support the hypothesis that the observed abrupt increases in serum calcium and phosphorus might cause the opposite CSF calcium shifts, the behavioral agitation and the increases in serum CPK frequently noted during acute psychosis.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Calcitonin; Calcium; Clinical Trials as Topic; Creatine Kinase; Dihydrotachysterol; Double-Blind Method; Female; Humans; Lithium; Male; Middle Aged; Phosphorus; Schizophrenia

Decreases in cerebrospinal fluid (CSF) calcium accompany mood elevation and motor activation in depressed patients undergoing treatment with ECT, lithium, and total sleep deprivation. Similarly, decreases in CSF calcium occur during acute psychotic agitation or mania. On the other hand, periodic recurrences of such agitated states are accompanied at their onset by transient increases in serum calcium and phosphorus. Several observations suggest that such serum ion shifts may trigger the more enduring and opposite shifts in CSF calcium and, in turn, the manic behavior. Progressive restriction of dietary calcium was earlier reported to mitigate and finally abolish both rhythmic rises in serum calcium and periodic agitated episodes in one psychotic patient. Lithium, which decreases the efficiency of alimentary calcium absorption, may function similarly. Conversely, a modest oral calcium lactate supplement (approximately one additional Recommended Daily Allowance of dietary calcium) seemed to slightly intensify agitation in six patients. Dihydrotachysterol (DHT), an analogue of vitamin D, which more exactly mimics the increase in both serum calcium and phosphorus, appeared in at least one periodically psychotic patient to trigger and opposite shift in CSF calcium. Moreover, in eight patients, manic symptomatology appeared de novo or grew significantly and substantially worse during 2 to 6 weeks of oral DHT administration. On the other hand, in 12 patients, subcutaneous injections of synthetic salmon calcitonin (SCT) decreased serum calcium and phosphorus, increased CSF calcium, and decreased agitation while augmenting depressive symptomatology. SCT also decreased quantified motor activity, frequency and severity of periodic agitated episodes, serum CPK and prolactin, and nocturnal sleep, while DHT or calcium lactate had opposite effects on the same parameters.

Topics: Animals; Bipolar Disorder; Calcitonin; Calcium; Circadian Rhythm; Creatine Kinase; Dihydrotachysterol; Humans; Lithium; Magnesium; Parathyroid Hormone; Phosphorus; Rats; Schizophrenia