Possible explanation for therapeutic action of lithium, and a possible substitute (methylene-blue)
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Biomedical subjects
Publications and source records attributed to G J Naylor.
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The effect of Vitamin C in manic-depressive psychosis was assessed by a double-blind, placebo controlled, crossover trial. Both manic and depressed patients were significantly better following a single 3 g dose of Vitamin C than following a placebo. Preliminary results of a double-blind, crossover comparison of normal vanadium intake with reduced intake in manic and depressed subjects are reported. Both manic and depressed patients were significantly better on reduced intake. These results are in keeping with the suggestion that vanadium may be an aetiological factor in manic depressive illness.
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A double-blind, placebo controlled, crossover trial of carbamazepine in 12 severely and profoundly mentally retarded, overactive adult patients is described. The trial lasted 7 months and those patients in whom overactivity was the dominant problem responded to some degree to carbamazepine with a reduction in overactivity. This was particularly so in patients in whom overactivity was accompanied by some elevation of mood. Patients in whom overactivity was part of a wider spectrum of multiple behaviour disorders showed a scatter of responses. There was no relationship between response to carbamazepine and the presence or absence of epilepsy. The trial identified a small group of mentally retarded patients in whom carbamazepine might be clinically useful.
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A group of bipolar manic depressive patients attending a routine lithium clinic were investigated. The results suggest that, when on treatment with lithium, manic depressive patients with a good prognosis tend to have a higher erythrocyte Na-K ATPase and higher plasma and erythrocyte lithium concentrations than those with a poor prognosis. There was no evidence to suggest that the erythrocyte: plasma lithium ratio was useful in predicting clinical response to lithium therapy. There was also a positive correlation between plasma lithium concentration and Na-K ATPase activity, confirming that in manic depressive subjects lithium produces a rise in erythrocyte Na-K ATPase activity.
Erythrocyte Na-K ATPase and sodium pump site numbers were estimated in groups of depressed, manic and recovered patients. The activity of Na-K ATPase per pump site was lower in the depressed group than in the recovered group. In the manic group Na-K ATPase was lower than that of the recovered group, whereas there was no difference in the pump site numbers. In the more severe manics the activity of Na-K ATPase per pump site was significantly lower than that of the recovered patients. Therefore, the change occurring in the erythrocyte membrane cation carrier in manic-depressive psychosis is probably in the activity of individual Na-K ATPase molecules and not in the number of Na-K ATPase molecules per cell.
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Erythrocyte and leucocyte numbers and cyclic AMP content were monitored weekly in a mentally defective short-cycle manic-depressive woman. The erythrocyte count remained relatively constant but cyclic AMP content when manic was significantly higher than when depressed, and the mood and biochemical data appeared to have the same periodicity, with coincident peaks and troughs. Total leucocytes were related to mood, with peaks in the manic phase. Mononuclear cyclic AMP content varied without relation to manic or depressive phases.
Emotional disturbance was assessed in a group of women in the first few days following childbirth and again 2 months and 1 year following childbirth; the clinical features are described. Variables such as social class, age and parity were not related to the level of emotional disturbance, but a history of marital problems, sexual difficulties, poor relationships with immediate family or disrupted family relationships in childhood were so related. Twenty-four hour urinary excretion of cyclic AMP (adenosine 3'5' cyclic monophosphate) was estimated in the same group of women on 2 occasions in the week following childbirth and again 2-3 months later in approximately one third of the original sample. Excretion of cyclic AMP in the few days following delivery was elevated compared with excretion 2-3 months later, and there was a significant rise in urinary excretion of cyclic AMP between the 1st and 2nd urine collections. Those women showing most emotional disturbance on the 3rd day after delivery and women indicating most mood change in the direction of becoming elated had the highest levels of cyclic AMP in the 2nd urine collection.
Approximately two thirds of a group of bipolar patients attending the routine lithium clinic suffered sid effects. These patients tended to have a lower plasma and erythrocyte lithium concentration and a lower erythrocyte/plasma lithium ratio than those who had no side effects. Explanations of this unexpected finding are discussed.
In two randomized double-blind controlled trials on 63 depressed female in-patients subject to recurrent affective disorder (bipolar and unipolar manic-depressive psychosis) lithium was shown to have major acute antidepressant effects. At the end of three weeks lithium produced more uniform improvement than did imipramine; lithium in combination with tryptophan (in the form of Optimax) was superior to tryptophan alone--the latter drug having no discernible antidepressant activity in this group of patients. Lithium did not produce an antidepressant effect until the second and third week of both trials.
A double-blind placebo-controlled trial of L-tryptophan, with pyridoxine and ascorbic acid, was carried out in 10 female patients suffering from mania. In contrast to earlier studies led by Prange and Murphy, L-tryptophan was found to be no better than placebo.
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Plasma levels of protriptyline have been determined in 30 patients undergoing antidepressant therapy. After 3 1/2 weeks treatment at dosage levels of 40 mg/day, protriptyline plasma levels ranged from 430 to 1430 nmol/l. During this period only two-thirds of the subjects had definitely achieved asymptotic concentrations. Single dose studies in 5 volunteers suggest that the volume of distribution of protriptyline shows little intersubject variation. The half life of the drug, however, may vary appreciably from subject to subject, ranging from 54 to 198 h. The effects of two sedatives on mean protriptyline plasma levels have been determined. Mean plasma levels for nitrazepam recipients are indistinguishable from those for patients receiving no night sedation. The mean plasma levels for a group of patients receiving sodium amylobarbitone were significantly reduced. The problems of choice and early adjustment of dosages in order to achieve satisfactory plasma levels is discussed. For practical purposes it is suggested that early values may be of predictive significance in allowing early dosage adjustments to be made.