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Biomedical subjects

T R Norman

Publications and source records attributed to T R Norman.

At least 19 recordsLinked to original sources

New pharmacological approaches to the management of depression: from theory to clinical practice.

A review of the clinical efficacy of four structurally distinct antidepressant drugs is presented. Their antidepressant activity can be rationalised within current pharmacological hypotheses of drug action, despite markedly different effects on "in vitro" testing. Fluoxetine, a specific serotonin re-uptake inhibitor, has proven safe, effective treatment for depressive illness and may have a role to play in the treatment of obsessive-compulsive disorder and panic attacks. While it has few of the anticholinergic side effects of the tricyclic antidepressants, nausea, tremor, headache, weight loss, nervousness and sweating are side effects most frequently reported. Minaprine, a compound with weak MAO inhibiting properties and effects on serotonergic receptors, has clinical efficacy in the treatment of depression based on several comparative studies. It is claimed that minaprine lacks anticholinergic and sedative properties. Moclobemide, a specific, reversible inhibitor of MAO-A, has been extensively evaluated in depressive illness. The major advantage of this agent over other irreversible, non-specific MAO inhibitors, is the significant attenuation of the so-called "cheese effect" with doses of tyramine likely to be encountered in foodstuffs. Rolipram, a phosphodiesterase inhibitor, represents a new approach to antidepressant treatment. Limited clinical data suggest that the drug may be an effective antidepressant with few side effects. The place of these agents in therapy is yet to be established.

Antidepressive Agents

Comparative bioavailability of orally and vaginally administered progesterone.

OBJECTIVE: To study the pharmacokinetics of progesterone (P) in healthy premenopausal female volunteers to compare the bioavailability of orally or vaginally administered hormone. DESIGN: Subjects were randomly allocated to receive either oral P or a vaginal pessary then crossed over to the alternate preparation 1 month later. SETTING: The study was conducted in outpatient setting. SUBJECTS: All subjects were healthy, normal female volunteers who underwent a physical and gynecological examination before the study. None were using oral contraceptives. Ten subjects (mean age 32.6 +/- 7.3 years) entered the study and all completed it. INTERVENTIONS: Progesterone was administered as 200 mg of micronized hormone or as a pessary containing 400 mg. MAIN OUTCOME MEASURE: Plasma levels of P were measured by radioimmunoassay to test the apriori hypothesis of similar bioavailability. RESULTS: Peak plasma P concentrations attained within 4 hours after oral administration ranged from 8.5 to 70.6 ng/mL, whereas after vaginal administration the peak levels were attained within 8 hours and ranged from 4.4 to 181.1 ng/mL. Considerable interindividual variation was noted. Area under the plasma concentration-time curve for the two formulations was not significantly different (F = 1.09; P greater than 0.1; ANOVA). CONCLUSIONS: The two formulations had similar bioavailability.

Administration, Oral

Panic disorder: a treatment update.

Panic disorder is characterized by unexpected, unprovoked attacks of cognitive symptoms (e.g., dread, fear) and physical symptoms (e.g., palpitations, trembling, shortness of breath). It is the most common anxiety disorder seen in clinical practice. Pharmacotherapy has been shown to be effective in controlling symptoms of panic disorder, although potential disadvantages (e.g., adverse drug reactions, withdrawal syndrome, dependency) must be carefully assessed and balanced against the advantages. Current data indicate that for panic disorder, benzodiazepines prescribed for more than a 6-month period are as effective as other forms of pharmacotherapy, i.e., monoamine oxidase inhibitors and tricyclic antidepressants. Generally, doses of benzodiazepines used for the treatment of panic are higher compared to those used for generalized anxiety disorder.

Alprazolam

Serotonergic effects of isatin: an endogenous MAO inhibitor related to tribulin.

A study of the acute effects of isatin, an endogenous MAO inhibitor related to tribulin, on rat brain serotonergic function was undertaken. A single dose of isatin significantly increased 5-HT concentrations in the hypothalamus and cortex but did not significantly alter 5-HIAA concentrations. Synaptosomal 5-HT uptake was unaffected but there was a trend for the number of 3H-ketanserin binding sites was to be decreased. The results of the study are discussed in terms of the relationship of isatin to tribulin and their possible causal role in stress.

Animals

Short-acting versus long-acting benzodiazepines: discontinuation effects in panic disorders.

An increasing body of evidence suggests that benzodiazepines--which have long been considered the drugs of choice in the treatment of various anxiety disorders due to their relative lack of side effects, lack of adverse drug reaction, their safety, and increased efficacy over other agents--are effective in the treatment of panic disorders. Originally, the benzodiazepines were believed to be devoid of dependence-inducing properties, even at high doses. Recent evidence, however, suggests that discontinuation of both high and normal doses of both short- and long-acting benzodiazepines generally results in similar withdrawal symptoms, including anxiety and sleep and perceptual disturbances. This article presents a brief review of benzodiazepine withdrawal, with an emphasis on the discontinuation of these drugs following treatment of panic disorders. In particular, short-acting and long-acting drugs may present different features following long-term treatment and withdrawal. Preliminary results from a study comparing alprazolam and diazepam are presented to illustrate this point in contrast to expectations: the problems associated with withdrawal of both agents were comparable.

Alprazolam

High-affinity platelet [3H]LSD binding is decreased in panic disorder.

Platelet [3H]LSD binding was measured in 15 patients with panic attacks and 15 controls. The mean (+/- SD) Bmax values of the patients (14.1 +/- 6.3 fmol/mg protein) and of the controls (18.5 +/- 4.7 fmol/mg protein) were significantly different (P less than 0.05, Mann-Whitney U-test). Mean (+/- SD) values of Kd for the patients (0.55 +/- 0.34 nM) and for the controls (0.51 +/- 0.12 nM) were not significantly different (P greater than 0.1, Mann-Whitney U-test). The results are discussed in terms of a serotonergic hypothesis of the aetiology of panic disorders.

Adult

Breastfeeding and the use of psychotropic medication: a review.

The advisability of continuing breastfeeding is an important issue for women with postpartum depression or psychosis. A review of the literature on psychotropic drugs in breast milk is presented. All of the major classes of psychotropic drugs (antidepressants, antipsychotics, antianxiety agents, lithium, hypnotics) have been shown to pass into breast milk following maternal ingestion. Generally, the doses to which children are exposed from breast milk, calculated from measured milk/plasma ratios, are small. Nevertheless most authors err on the side of caution and suggest that breastfeeding be avoided. There is inadequate research on the excretion of drugs into breast milk and the effects on the infant.

Breast Feeding

A portable light source for bright light treatment.

A novel, portable, inexpensive bright light source is described. This unit, which has been demonstrated to exhibit physiological effects similar to those of the more conventional light boxes, offers a less restrictive home treatment for patients with seasonal affective disorder and sleep disorders.

Adult

Pharmacokinetic and pharmacodynamic effects of a single nocturnal dose of alprazolam.

Six healthy volunteers participated in a study of the pharmacokinetic and psychomotor effects of a single dose of 2 mg of alprazolam compared to placebo when given at night. Alprazolam reached a maximum concentration in the plasma between 0.5 and 2.5 h after the dose. It was extensively distributed to the tissues as shown by the large apparent volume of distribution (1.42 l/kg) and slowly eliminated (t1/2 = 13.7 h). Significant impairment of choice reaction time occurred 1 and 11 h after the dose of alprazolam compared to placebo. Critical flicker fusion was also impaired after alprazolam but the difference from the placebo administration did not reach significance.

Administration, Oral

Plasma concentrations of melatonin in panic disorder.

Nocturnal plasma melatonin concentrations were measured in seven patients with panic disorder and eight healthy control subjects. The five patients who had never received psychotropic medication had significantly greater melatonin concentrations from 4:00 a.m. to 7:00 a.m. than the control subjects. In addition it is possible that a phase delay occurred in these unmedicated patients. The findings are discussed in terms of previous studies showing increased melatonin in manic patients and the effect of intense stress on melatonin synthesis. The two patients who had been medication free for only 1 week showed a decreased melatonin rhythm, which is consistent with previous findings in medicated patients.

Adult

Current treatment concepts in depression.

Depression is a common disorder. While depressive symptoms are often transient and may be regarded as normal, 10 per cent of the population suffers depressive symptoms of sufficient severity and duration to be diagnosed as suffering a depressive illness.

Antidepressive Agents

Quantal melatonin suppression by exposure to low intensity light in man.

Plasma melatonin concentrations were examined following three relatively low intensities of artificial light. Six normal, healthy control subjects were all exposed to (a) 200 lux, (b) 400 lux and (c) 600 lux for a three hour duration from midnight to 0300 h. Blood was also collected on a control night where light intensity was less than 10 lux throughout. Significant suppression of melatonin was observed following light of 400 lux and 600 lux intensity when compared to the control night (p less than 0.05; Mann-Whitney U-test). 200 lux light did not produce a statistically significant melatonin suppression when compared with control samples. Each light intensity produced its own individual maximal melatonin suppression by one hour of exposure. Increased duration of exposure to the light had no further influence on melatonin plasma concentrations. These data confirm a dose response relationship between light and melatonin suppression, and indicate that there is no reciprocal relationship between the effects of light intensity and the duration of exposure on maximal melatonin suppression in man.

Adult

Platelet serotonin uptake in panic disorder patients: a replication study.

Platelet serotonin uptake was measured in 29 patients with DSM-III panic disorder or agoraphobia with panic attacks and compared to values obtained in 23 controls. Both the affinity constant (Km) and the maximal rate of uptake (Vmax) were determined in a buffered medium using 14C-serotonin. Patients and controls did not differ significantly with respect to age or Km values. A statistically significant difference was observed for Vmax (mean +/- SD = 65 +/- 22 pmol/10(8) platelet/min in patients vs. 44 +/- 13 pmol/10(8) platelets/min in controls). This finding suggests an overactivity of peripheral serotonergic function in panic disorder, which may also imply a similar dysfunction centrally.

Adolescent