Amitriptyline versus haloperidol in borderlines: final outcomes and predictors of response.

The authors report the final results of a 4-year study of amitriptyline and haloperidol in 90 symptomatic borderline inpatients. Medication trials were double-blind and placebo controlled and lasted 5 weeks. Haloperidol (4-16 mg/day) produced significant improvement over placebo in global functioning, depression, hostility, schizotypal symptoms, and impulsive behavior. Significant effects of amitriptyline (100-175 mg/day) were generally limited to measures of depression. Factor analysis identified three symptom change patterns: a global depression, hostile depression, and schizotypal symptom pattern. Medication effects favoring haloperidol were most prominent for hostile depression. Variables predicting favorable response to haloperidol included severity of schizotypal symptoms, hostility, and suspiciousness. Schizotypal symptoms and paranoia predicted poor outcome on both depression patterns with amitriptyline. Placebo effects were most prominent on acute state symptoms, with severe character traits predicting poor response.

The self-reported effects of PCP on human aggression.

The elicitation of violent of psychotic behavior by phencyclidine (PCP) administration is well documented. There are indications, however, that behavioral responses to PCP may differ among PCP users as a function of background or personality characteristics. The present study examined 35 male jail inmates with histories of PCP use. Estimates of the nature and extent of drug use and self-reports of previous psychiatric hospitalizations were obtained in these subjects. The Buss-Durkee Hostility Inventory was modified to reflect behaviors under the two simulated conditions of "No PCP" and "PCP" use. Results showed that PCP use was related to increased levels of hostility in our subjects when present age, age of first use, the frequency of use and suspicion and assaultive behavior when not using PCP was considered. Also, subjects with a history of psychiatric hospitalizations reported higher levels of assault when using PCP than those without psychiatric histories. These data suggest that the self-reported behavioral results of PCP use are associated with certain personality traits and background features.

An efficacy study of isocarboxazid and placebo in depression, and its relationship to depressive nosology.

Isocarboxazid and placebo were evaluated in 130 anxious depressives. Drug was superior to placebo on depression, anxiety, interpersonal sensitivity, and global measures, and on symptoms of hostility, anxiety, obsessiveness, and psychological-cognitive components of depression. There were no significant differences between treatment effects on psychomotor and typical vegetative symptoms. Isocarboxazid was more effective than placebo in major, but not in minor, depression. It was significantly more effective in depression classified as endogenous depression or melancholia by various diagnostic criteria. Drug was more effective than placebo in atypical depression with vegetative reversal and in Brief Psychiatric Rating Scale (BPRS)-derived profiles of anxious and hostile depression; there were no drug-placebo differences in atypical depression without vegetative reversal, or in BPRS retarded and agitated/excited depression. Interpersonal sensitivity emerged as an important drug-responsive dimension.

Zuclopenthixol and melperon in the treatment of elderly patients: a double-blind, controlled, multi-centre study.

A double-blind study was carried out in 53 elderly patients in 6 geriatric nursing homes to assess the effectiveness of the neuroleptics, zuclopenthixol and melperon (flubuperone), in the relief of restlessness, aggressiveness and other such symptoms. The initial daily dose was 4 mg zuclopenthixol or 75 mg melperon, increased if necessary over the treatment period of 4 weeks. Assessments were made on entry and after 1, 2 and 4 weeks of treatment of the overall severity of illness and of individual symptoms. The results showed that there was significant improvement in the condition of patients in both treatment groups and a significant reduction in mean total as well as in the main single symptom scores. These changes were already apparent after 1 week of treatment. Although there was a tendency for faster improvement in the zuclopenthixol group, there were no significant differences between the groups in any of the parameters assessed. Side-effects were few and generally mild and transient.

Effects of beta-adrenergic stimulation and blockade on cardiovascular reactivity, affect, and type A behavior.

The present study examined the acute effects of drugs that stimulate or block sympathetic nervous system activity on components of Type A behavior, affect, and cardiovascular responses to mental stressors. Either propranolol (a beta-adrenergic blocker), isoproterenol (a beta-agonist), or placebo was infused intravenously at different times in 12 healthy males. In two sessions, placebo (saline) was administered first, followed by a structured interview, challenging mental arithmetic test, and completion of affect scales. The procedure was then repeated with one of the active drugs, presented in counterbalanced order. Results indicated reliable drug effects on both heart rate (HR) and systolic blood pressure (SBP) reactivity to the tasks, with change scores to the tasks markedly increased by isoproterenol. Anxiety and hostility ratings paralleled results for HR and BP, with much of this effect being due to higher affect ratings for isoproterenol. The effect of the drugs on Type A behavior was unexpected, with global Type A and several components lowered by isoproterenol and unaffected by propranolol. These data are discussed in terms of the interfering effects of anxiety on Type A speech components. The influence of isoproterenol on affect and reactivity might reflect the physiologic action of a beta 2-adrenergic positive feedback loop which increases release of endogenous norepinephrine, and/or potentiating effects of emotion on reactivity to stress.

Clinical and biochemical effects of verapamil administration to schizophrenic patients.

We administered verapamil hydrochloride, a calcium channel antagonist, to seven chronically ill schizophrenic patients for five weeks under double-blind, placebo-controlled conditions. No therapeutic effect was noted. Worsening in hostile and uncooperative behaviors and a syndrome of heightened emotional tone was observed during verapamil treatment and during the postverapamil placebo period. Verapamil produced significant increases in cerebrospinal fluid (CSF) and plasma levels of homovanillic acid and in plasma levels of prolactin, as well as significant decreases in plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol. Verapamil and its active metabolite, norverapamil, were partitioned into CSF with CSF/plasma ratios of 0.06 and 0.04, respectively. The lack of therapeutic effects of verapamil in schizophrenic patients differs from earlier reports of its usefulness in treating manic patients. The biochemical and clinical data from our study suggest the possibility that verapamil exerts behaviorally relevant central nervous system activity in schizophrenic patients.

Combination of psychotherapy and drugs in the treatment of neurosis. A controlled comparison of bromazepam and thioridazine.

Eighty out-patients with neurotic disorders were studied in an integrated treatment model combining psychotherapy and psychotropics in a "conjoint marital therapy" setting. The spouses, who seemed a healthy group, were used as reporters, as controls and as participants in the psychotherapy. The pharmacological trial was a double-blind, cross-over study, comparing bromazepam and thioridazine after a placebo period. Bromazepam was more effective in controlling different anxiety symptoms and demonstrated more potent activating properties than thioridazine. Hostility symptoms, however, responded better to thioridazine. These findings were confirmed by ratings performed by patients, spouses and the investigator. Differences in drug preference and drop-out rate showed the same tendency. Nine weeks' continuous treatment did not change the differences found in the cross-over study. No pharmacological rebound symptoms were observed after drug withdrawal. The personality of the spouses was related to the outcome in the patients. Moreover, there was an obvious positive interaction between the psychotherapy given and the drug treatment.

A comparison of parenteral loxapine and haloperidol in hostile and aggressive acutely schizophrenic patients.

In a parallel groups, double-blind study, 54 acutely psychotic schizophrenics were given loxapine or haloperidol parenterally for 24 to 72 hours, then orally for a total study period of up to 10 days. Dosage ratios of loxapine to haloperidol ranged from a minimum of 2.7:1 to a maximum of 4.4:1. Both groups showed significant and rapid improvement from baseline. Forty-eight percent of the loxapine patients and 33% of the haloperidol patients achieved and maintained a global severity of illness rating of mild or better. By the end of the study, 84% of the loxapine patients and 63% of the haloperidol patients had achieved an improvement rating of moderate or marked. This difference approached significance (p less than .10). The most frequently reported adverse experiences were dystonic reactions and akathisia. The number and severity of adverse experiences did not differ significantly between drug groups. Intramuscular loxapine was at least as effective as haloperidol in the initial management of hostile and aggressive schizophrenic patients. The maintenance of therapeutic response after conversion to oral concentrate was comparable with the two drugs.

Behavioral indications for phenothiazine and benzodiazepine tranquilizers in dogs.

In a controlled study on 18 caged dogs, the effects of 2 psychoactive drugs on friendliness, excitability, and fearfulness were systematically and quantitatively evaluated. Diazepam was selected to represent the benzodiazepine group, and chlorpromazine represented the phenothiazine group. Diazepam was more effective in suppressing signs of fear than was chlorpromazine. Diazepam increased measures of excitability, whereas chlorpromazine had opposite effects.

Reduction of distress in hyperprolactinemia with bromocriptine.

In a double-blind placebo-controlled crossover study of bromocriptine in eight hyperprolactinemic patients, self-rated distress decreased and well-being increased parallel with the fall in prolactin levels; for the majority of measures the differences were significant.

Sex steroids and affect in the surgical menopause: a double-blind, cross-over study.

The effect of estrogen and/or androgen on mood in surgically menopausal women was investigated with a prospective, double-blind, cross-over design. Oophorectomized women who received either estrogen (E), androgen (A), or a combined estrogen-androgen preparation (E-A) parenterally attained lower depression scores during both treatment phases compared to a placebo group (PL), coincident with their higher plasma estrogen and testosterone levels. When steroids were withdrawn, depression scores of all oophorectomized women were significantly higher than those of a hysterectomized control group with intact ovaries (CON). The A group also had higher hostility scores than the E, PL, and CON groups. These data provide evidence of a covariation between circulating levels of estrogen and testosterone and certain affects in healthy women.

[Pharmaco-ethological analysis of agonistic behavior between resident and intruder mice: effects of psychotropic drugs].

The present study was conducted to investigate the effects of psychotropic drugs on agonistic behavior between resident and intruder mice. The effects of four doses of the following drugs were assessed in either resident or group-housed intruder mice: chlordiazepoxide (0, 5, 10 and 20 mg/kg, i.p.), haloperidol (0, 0.25, 0.50 and 0.75 mg/kg, i.p.) and imipramine (0, 5, 10 and 20 mg/kg, i.p.). Residents and intruders were drugged on alternate test days, and all animals received different sequences of each of the drug conditions according to a random schedule. The injection-test interval was 30 min. When resident mice were treated with chlordiazepoxide the resident's aggressive episodes (sideways posture, attack bite, tail rattle) were significantly suppressed. Both haloperidol and imipramine also showed a similar suppressive effect on the resident's aggressive episodes, but haloperidol significantly suppressed locomotor activity at all doses. When intruder mice were treated with chlordiazepoxide, attack bites by untreated residents were significantly increased in a dose-dependent manner, and the frequency of defensive upright posture displayed by intruder animals were significantly decreased. Haloperidol and imipramine did not alter resident's behavior and intruder's upright posture when intruders were drugged. The results suggest that chlordiazepoxide has specific effects on both the hostility of the resident and the anxiety of the intruder, differing from haloperidol and imipramine.

Differential effects of diazepam and pentobarbital on mood and behavior.

The effects of administering moderately high doses of diazepam and pentobarbital sodium for five consecutive days to subjects with histories of sedative drug abuse were examined. The two drugs produced similar dose-related effects on psychomotor performance, daytime sleeping, and ratings of magnitude of drug effects. Diazepam, but not pentobarbital, produced dose-related decreases in staff ratings of subjects' mood and social interactions and increases in staff ratings of subjects' hostility, complaining, and unusual behavior. During the placebo washout periods that followed drug administration. diazepam, but not pentobarbital, was associated with carry-over effects. The diazepam-produced deterioration in mood and social behavior was a subtle effect observed in a population for which usual therapeutic indications were lacking and at higher than usual therapeutic doses. The syndrome may, however, occur with long-term diazepam use or misuse in therapeutic settings and, hence, warrants clinical awareness in monitoring the course of treatment.

Alcohol, affect, and the disinhibition of verbal behavior.

A study was conducted to investigate the effects of acute alcohol administration on affective states and verbal behavior during the ascending and descending limbs of the blood alcohol curve. Sixteen male social drinkers were given alcohol (1.0 g/kg) or placebo in a double-blind crossover research design. Subjects tested while blood alcohol levels (BAL) were ascending close to peak concentration (0.11 g%) described themselves as more elated, friendly, and vigorous than when tested under placebo conditions. As BAL declined, subjects described themselves as more angry, depressed, and fatigued. Cognitive confusion, hostile verbal interaction, and aggressive thematic content were also greater during alcohol intoxication, but these measures were unrelated to direction of change in the BAL curve. It was concluded that (1) the effects of alcohol on affect are biphasic and are closely related to direction of change in the BAL curve, (2) the disinhibition of certain types of verbal behavior is related neither to affective state or to direction of the BAL curve, and (3) the perception of cognitive disorientation may mediate the effects of alcohol on those behaviors normally suppressed by various controlling influences.

Loxapine succinate as initial treatment of hostile and aggressive schizophrenic criminal offenders.

The efficacy and safety of loxapine were evaluated in 18 acutely ill schizophrenic criminal offenders in the Essex County Jail. The offender patients were treated for three days with intramuscular loxapine (25 mg three or four times a day), followed by seven days of oral concentrate (up to 150 mg/day in three or four divided doses). Psychiatric status was determined with the Brief Psychiatric Rating and the Clinical Global impression scales at the time of admission, after 8, 24, 48, and 72 hours, amd on days 7 and 10 of medication. Three patients did not complete treatment: one was released on bail after 24 hours of therapy, and the other two had adverse reactions (tongue swelling and muscle spasms, each in one patient) which required cessation of treatment. Statistically significant improvement in both rating scale results was evident as early as 8 hours after treatment began. By day 10, all Brief Psychiatric Rating Scale items and factors and the Clinical Global impression results were statistically improved over baseline measurements. At the end of the study, 87 per cent (13/15) of the patients were well enough to cooperate with their attorneys and understand the procedures of the court. Adverse effects (generally extrapyramidal) appeared in four of 18 patients during parenteral administration and in two of 15 patients during oral therapy.

The effects of a provocation on aggression for three types of alcohol users.

Investigated the effects of a provocation on aggression for three types of alcohol users. The Alcohol Use Inventory was used to select 30 light-moderate and 30 moderate drinkers. Thirty abstainers were selected as a control group. Half of each group was assigned randomly to one of two treatments, a provocation or a no-provocation. After treatment, each S completed the Adjective Rating Form (ARF) verbal aggression scales and the Multiple Affect Adjective Checklist (MAACL). The results of this study indicated that, for both instruments, the provocation elicited significantly more feelings of hostility and verbal aggression than the no-provocation. However, there were no significant level effects, nor was there a significant interaction between level of drinking and presence of a provocation. The failure to find significant level effects was attributed to the abstainers' scores. With the abstainer category excluded from the analysis, additional findings resulted in significant level effects for the MAACL hostility scales, but not for the ARF verbal aggression scales. It was recommended that future studies investigate risk factors of abstinence and eliminate the abstainer category as a control.