William M. Petrie

Compulsive water drinking treated with high dose propranolol.

A patient with recurrent, life-threatening water intoxication secondary to compulsive water drinking is described. This patient responded well to nearly 1 g of propranolol daily with a decrease in her drinking behavior, reduced sensation of thirst, and a reduction in her delusional thinking. The rationale for the choice of propranolol with this patient is reviewed.

Vitamins in psychiatry. Do they have a role

SummaryDeficiencies of specific vitamins produce consistent symptoms of psychiatric disorder. Thiamine deficiency, which is common in alcoholism, can produce confusion and psychotic symptoms, in addition to neurological signs. Vitamin B12 and folate deficiency may contribute symptoms of disorientation, depression or psychosis; their measurement is a part of routine dementia work-ups. Pyridoxine deficiency results in seizures, although the effects of exogenously administered pyridoxine are not clearly understood in depression and anxiety — the disorders in which it is most frequently used clinically.The use of vitamins has been most prominent in psychiatry in the treatment of schizophrenia, where large doses of nicotinic acid were initially given alone and later combined with other vitamins and minerals. Several theoretical models were described to support the use of vitamins in schizophrenia. These included: the parallels of schizophrenia to the psychiatric symptoms of pellagra; hypotheses of a defect in adrenaline metabolism; and the accumulation of psychotoxic substances which produce psychotic symptoms. Initially, positive results were reported over 30 years ago, but have not been replicated by thorough investigations. An extensive series of comprehensive placebo-controlled trials failed to show efficacy for any of the vitamin therapies tested.Although clearly less effective than antipsychotic drug treatment, vitamin therapy is not without risks — adverse effects have been reported with nicotinic acid, pyridoxine and vitamin C. Although the possible role of vitamins has played an important part in the development of biological psychiatry, vitamin therapy is no longer extensively practised, and claims for its efficacy have not been supported by objective scientific evidence.

Viloxazine in the treatment of endogenous depression. A standard (amitriptyline) controlled clinical study.

In a double-blind clinical trial with 20 patients suffering from endogenous depression statistically significant changes (improvement) were present in the scores of all assessment instruments. Although no statistically significant differences occurred between the groups, significant improvement on the HAM-D occurred earlier for amitriptyline and significant improvement occurred earlier on HAM-A for viloxazine. 2 patients were discontinued due to adverse reactions; one for nausea and vomiting while receiving viloxazine and one for paroxysmal atrial tachycardia while receiving amitriptyline. The same number of TES occurred for each group with seven unique to viloxazine (numbness, tingling, palpitation, ejaculation difficulty, nausea/vomiting, diarrhea, epigastric pain and gustatory disturbances) and seven unique to amitriptyline (insomnia, irritability, syncope, tremor, nasal congestion, orthostatic hypertension and paroxysmal atrial tachycardia). Other than for 1 patient who developed syncope and orthostatic hypotension and the patient who developed paroxysmal atrial tachycardia, there were no clinically significant changes in pulse rate, blood pressure and weight. There were no clinical laboratory findings with either drug that were judged to be pathological.

The use of nicotinic acid and pyridoxine in the treatment of schizophrenia.

As part of the Canadian Mental Health Association Collaborative Study, the hypothesis that combined administration of nicotinic acid and pyridoxine has greater therapeutic effects than the component drugs in chronic schizophrenic patients was tested. This could not be substantiated in a 48-week study in which supplementation of neuroleptic treatment with a single vitamin, i.e., nicotinic acid or pyridoxine, produced significant therapeutic changes, while supplementation with both vitamins did not.

Systematic studies with amoxapine, a new antidepressant.

Amoxapine, a tricyclic dibenzoxazepine is an antidepressant which in the dosage range of 150-300 mg/day is notable for its rapid onset of action. Because of the rather long, approximately 30-hour, half-life of 8-hydroxyamoxapine, the active metabolite of amoxapine, the possibility was raised that amoxapine therapy may be carried out with single daily dosages. Such a dosage schedule may improve compliance and, if appropriately timed, decrease perception of some of the unwanted effects of the drug. To test the hypothesis that there may be no disadvantages and perhaps even advantages of a once-a-day regimen as compared to a divided dosage schedule, a 6-week double-blind clinical trial was carried out in 35 hospitalized patients with major (18 patients) and minor (17 patients) depressive disorders. While no statistically significant difference was found in overall therapeutic and adverse effects between the groups treated with single or divided daily doses, onset of therapeutic effect appeared a bit faster in the group treated with single daily doses. Of particular relevance for drugs which can be given in single daily doses is their effect on psychomotor performance tests. In view of the findings that a once-a-day dosage regimen with amoxapine may have advantages over divided daily doses, a second study was carried out in which the effects of amoxapine (50 and 100 mg) were compared to an inactive placebo and amitriptyline (50 mg) with and without ethanol in 8 normal male volunteers. The study was double-blind and followed a latin square design. Since the effects of amoxapine on motor reflex, visual-motor coordination and depth perception did not differ significantly from placebo, the results suggest that the effects of amoxapine on the performances measured are clinically insignificant. No significant interaction with ethanol was noted.

A collaborative study of a new antidepressant, viloxazine, in neurotic and endogenous depressives.

In a multicenter series of trials, viloxazine was compared with imipramine, amitriptyline, doxepin and placebo in 123 neurotic and endogenous depressive inpatients and outpatients. While significant period effects reflecting improvement were obtained on the majority of efficacy variables, no significant differences were obtained among the treatment groups or depressive types. Imipramine and amitriptyline exhibited more anticholinergic adverse reactions; while, viloxazine exhibited greater CNS effects. Dizziness and nausea were much more frequent in neurotic depressives which may be related to their psychopathology.

Psychoses with propranolol: a case report

Functional and organic psychoses have been reported in association with propranolol therapy. The authors report a rare occurrence of both types of psychoses in the same individual at two different times during propranolol therapy.

The effects of amoxapine and ethanol on psychomotor skills related to driving: A placebo and standard controlled study

Abstract 1. 1. Eight normal male volunteers were tested under eight different treatment conditions: amoxapine 50 and 100 mg, amitriptyline 50 mg. and placebo—each condition with and without ethanol—(1.3 g/kg body weight), utilizing a double-blind repeated measures latin square design balanced for carry-over. Motor reflex, pursuit rotor and depth perception tests were conducted when blood levels of the active drugs and alocohol were simultaneously at or near peak. 2. 2. Analyses revealed significant effects of amitriptyline and ethanol on the motor reflex and pursuit rotor but not for depth perception tests, and the effects of ethanol appeared to be potentiated by amitriptyline on the pursuit rotor test; this was not true for amoxapine. 3. 3. Although the effects of 100 mg of amoxapine were consistently greater than for 50 mg or placebo, these differences did not reach a statistical significant level. 4. 4. Since amoxapine did not differ significantly from placebo, these results suggest that the effects of amoxapine on driving skills may not be as pronounced as those produced by amitriptyline.

Viloxazine in the treatment of depressive neurosis: a placebo and standard (imipramine) controlled clinical study.

In a 4-week double-blind trial, 33 patients with depressive neurosis were randomly assigned to either viloxazine, imipramine or placebo. Statistically significant improvement was observed in all treatment groups. Imipramine exhibited significant improvement earlier in depressive symptoms, while viloxazine showed significant improvement earlier in anxious symptoms. The same frequency of treatment emergent symptoms occurred in the treatment groups. Premature termination as a consequence of adverse reactions was required in only 1 viloxazine and 1 placebo patient.

Drug-Induced Psychosis

Bonhoeffer (1910) initially made the distinction between endogenous and exogenous psychoses, suggesting that toxic-metabolic factors can produce symptoms similar to those of functional psychoses. Drug-induced psychoses have in the last 30 years been observed with a vast array of prescribed and illicit pharmacological agents. Accordingly, extensive work has been done in the past three decades, attempting to elucidate neurobiological mechanisms that underlie both natural and drug-induced psychotic states. Indeed, the current explosive growth in biological psychiatry was heralded by early hypotheses relating molecular structures of hallucinogens to those of endogenous biogenic amines (Osmond & Smythies, 1952). We (Ellinwood & Petrie, 1976, 1979) have previously described the complex interaction between clinical and pharmacological factors that affect behavioral-symptom outcomes of abused drugs in a clinical setting. In this chapter we address only the pharmacological aspect of illicit psychotomimetic drugs currently in popular usage, with specific focus on central neuronal mechanisms that are common to both the different drug categories and the natural psychoses.