Alyson J. Bond

Residual effects of hypnotics.

Ten normal subjects were tested on a large battery of physiological and psychological tests 12 h after a hypnotic dose of butobarbitone sodium (100 or 200 mg) or nitrazepam (5 or 10 mg) and compared with a placebo. The subjects received all five treatments in a balanced design. The tests used included self-ratings, the electroencephalogram, the auditory electroencephalographic evoked response, reaction time, tapping, card-sorting and the digit symbol substitution test. Both drugs were effective hypnotics according to the ratings but butobarbitone had more subjective “hangover” the following morning. The electroencephalogram showed significant changes after both drugs but the evoked response was affected most by 10 mg nitrazepam. The psychological tests showed some dose-related impairment after both drugs. Bioassay statistics suggested that with respect to these residual effects the relative potency of nitrazepam to butobarbitone was 27∶1.

The residual effects of flurazepam

Eight normal subjects were tested on a large battery of physiological and psychological tests 12, 15 and 18 h after a hypnotic dose of butobarbitone sodium (150 mg), flurazepam (15 or 30 mg) or a placebo. The subjects received all four treatments in a balanced design. The tests included self-ratings of mood, the electroencephalogram, the auditory electroencephalographic evoked response, reaction time, the digit symbol substitution test and the symbol copying test. Both drugs were effective hypnotics according to the ratings but they also influenced “mood” the following day. The electroencephalogram and the evoked response showed significant changes up to 18 h after both drugs. The psychological tests were only affected 12 h after the drugs.

Drug- Induced Behavioural Disinhibition

SummaryBehavioural disinhibition implies the loss of restraint over some form of social behaviour. Such disinhibition can be drug induced and, on rare occasions, lead to extreme acts of aggression or violence. Examples of behavioural disinhibition are often considered paradoxical and rare reactions to drugs, but they may in fact be a more severe behavioural manifestation of a general effect that the drug has on emotions and behaviour. However, the incidence of drug-induced behavioural disinhibition varies considerably and cannot be estimated accurately, as accounts stem mainly from case reports rather than from controlled clinical trials. Adverse effects of drugs are rarely, if ever, the sole focus of clinical studies, although they are now monitored more rigorously in controlled trials.There are numerous anecdotal case reports in the literature of behavioural disinhibition occurring during administration of benzodiazepines, and recent controlled trials have addressed this issue. The incidence varies with the population studied, but tends to be higher in patients with pre-existing poor impulse control. Alcohol (ethanol) potentiates the disinhibiting effect of benzodiazepines. Aberrant forms of disinhibited behaviour may be accompanied by memory loss.Disinhibition has also been reported after treatment with tricyclic antidepressants, and reports are now appearing that describe disinhibition in patients who have been treated with selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors. These include incidents of akathisia, suicidal urges, agitation, hyperactivity and mania. They are more prevalent in children and those with learning disabilities.Disinhibition is rare with antipsychotics and non-benzodiazepine anticonvulsants but some isolated case reports contain descriptions of such reactions with newer compounds.The most important drug variable in drug-induced behavioural disinhibition is dosage, although mode of administration is also important. Discontinuation of the drug is usually expected to resolve behavioural reactions, but in certain cases drug withdrawal may precipitate a reaction. In order to minimise drug-induced behavioural disinhibition, it is essential to always use the minimum dosage necessary, to increase the dosage gradually and to monitor the effects carefully. Multiple drug use should be avoided whenever possible.

Comparative Psychotropic Effects of Metoclopramide and Prochlorperazine in Normal Subjects

May-June, 1975 449 M ETOCLOPRAMIDE (AHR-3070, Maxolon*) was introduced for use in man about ten years ago. It is chemically related to procainamide and is available in oral, intramuscular, and intravenous form for administration. It is useful for increasing gastrointestinal peristalsis while relaxing the duodenal bulb.1 It is also indicated for control of nausea and vomiting associated with general anesthesia and

Memory functions, alprazolam and exposure therapy: a controlled longitudinal study of agoraphobia with panic disorder

Benzodiazepines (BZs) produce transient anterograde amnesia when given to normal subjects. The present longitudinal study assessed whether BZs impair memory functions in a clinically anxious group. Eighty-two agoraphobics with panic disorder were randomly allocated to one of four treatment groups resulting from a combination of two drug treatments (alprazolam or placebo) and two psychological treatments (exposure or relaxation). Of these, 38 subjects were assessed on a range of objective and subjective indices of memory and mood at three time points: before treatment, after 8 weeks of treatment and again at 24 weeks when patients had been free of medication from 5-8 weeks. Alprazolam produced pronounced impairments on a word recall task. At the 24-week medication-free follow-up, alprazolam patients were still impaired on the task compared with placebo patients. Alprazolam did not impair performance on an implicit memory task and did not affect digit span. Differences between psychological treatments emerged mainly in subjective memory effects. Findings are discussed in terms of the specificity of BZ-induced amnesia and differential tolerance to the varying effects of BZs. Implications are drawn out for the patients ability to function optimally in daily life while taking alprazolam.

Impaired performance and sedation after a single dose of lorazepam.

In a double-blind cross-over study using normal student volunteers, the effects of 1 and 2.5 mg lorazepam on self-rated mood and bodily symptoms, as well as performance in a number of tests were assessed. Both doses significantly increased self ratings of physical and mental sedation, the effects being more marked 4 h after drug administration than after 1 h. Lorazepam impaired simple reaction time, verbal learning, number cancellation, symbol copying and performance in the digit-symbol substitution test. The impairments were greater with the 2.5 mg dose and were more marked 4 h after drug administration than after 1 h.

Differential effects of oxazepam and lorazepam on aggressive responding

Two doses of two very similar benzodiazepines (oxazepam 15 and 30 mg: lorazepam 1 and 2 mg) and placebo were compared 4 h post-administration on a competitive reaction time task designed to measure behavioural aggression. Forty-five subjects were assigned randomly to five independent drug groups. Subjective ratings of mood, anxiety and aggression were completed pre- and post-drug and post-task. Oxazepam and lorazepam had very similar subjective effects, but the higher dose of lorazepam increased aggressive responding on the task more than any other treatment. This may be related to the different ceiling efficacies of the two benzodiazepines.

Assessment of attentional bias and mood in users and non-users of anabolic-androgenic steroids.

Forty-six male strength athletes took part in a study to measure the effects of anabolic-androgenic steroids on attentional bias to aggressive cues. They were 16 current users of anabolic steroids, 16 former users and 14 non-users. Testosterone, deca-durabolin and anadrol were the three most commonly taken steroids during the last cycle. Users generally took 2-3 drugs during each cycle; the average cycle lasted 8-11 weeks and they had completed 3-4 cycles. The subjects completed visual analogue scales of current feelings and were presented with a modified Stroop Colour Word Conflict Task containing sets of neutral, verbally aggressive and physically aggressive words. Current users tended to rate themselves more negatively. Users took longer than former users to name the colours of all word sets but there were no significant differences between word sets. Therefore, attentional bias did not differ between groups but current steroid use produced subtle mood changes and slowed performance compared to users not currently taking steroids.

Clinical comparison of anxiolytic drug therapy

Twenty outpatients suffering from chronic anxiety states completed a trial of anxiolytic drug therapy. They each received five treatments: amylobarbitone sodium, chlordiazepoxide, diazepam, medazepam, and a placebo in flexible dosage in a fully balanced design, using doubleblind procedures. They were assessed on the Hamilton rating scale for anxiety after a period of two to four weeks on each of the treatments and they completed self-ratings every three days. The selfratings were composed of at least three prime symptoms chosen by the patient himself and phrased in his own words as well as ‘loss of appetite’ and ‘insomnia’. Neither placebo nor amylobarbitone produced any substantial improvement from pre-drug levels of anxiety but all three benzodiazepines produced significant and very similar decreases in both Hamilton ratings and self-ratings. These two measures also correlated highly. The majority of the patients continued with medazepam at the end of the formal trial.

Selective processing of food- and body-related information and autonomic arousal in patients with eating disorders

Both attentional bias (using the modified Stroop Task) and autonomic reactivity (skin conductance level) to food- and body-related information were assessed in 25 patients with eating disorders (15 patients with anorexia, 10 patients with bulimia) and 18 women controls. Patients with anorexia showed the greatest interference in color-naming food-related words. However, on this occasion there were no differences in body condition, probably because of heterogeneity of clinical samples and because the control group were staff members, so the target information was very familiar to them. The groups differed in their autonomic reactivity while performing the Stroop, the patients with anorexia responded with higher skin conductance ( p