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Biomedical subjects

D B Montgomery

Publications and source records attributed to D B Montgomery.

9 recordsLinked to original sources

Pharmacotherapy in the prevention of suicidal behavior.

Prevention or reduction of suicide remains a serious challenge for the medical community. Psychotherapeutic and psychosocial interventions have not been shown to reduce the incidence of suicide attempts and analytic psychotherapy has been shown to increase suicidal behavior. The efficacy of pharmacotherapy in reducing suicide attempts in patients with a history of repeated suicidal behavior has been shown with low doses of the neuroleptic agent flupenthixol compared with placebo. Supporting findings have been reported with trifluoperazine. There is evidence to suggest that some antidepressants may not be neutral in their effect on suicidal behavior. Maprotiline, for example, was associated with an increase in suicide attempts compared with placebo in a large long-term treatment study despite its significant efficacy in preventing relapse of depression. Differential lethality indices taken from large community studies support the notion that noradrenergic drugs such as maprotiline, desipramine, and nortriptyline are associated with a higher than expected incidence of death from overdose, and the suicide-provoking potential may relate to some noradrenergic property. The studies of serotonergic antidepressants do not suggest that they are suicide-provoking agents; rather they appear to be neutral or protective. Prospective prophylactic studies are needed to test the ability of potential treatments for the reduction of suicidal behavior.

Antidepressive Agents

A new magnetic technique for the treatment of giant retinal tears.

Using surgical techniques similar to those for closed vitreous surgery, we introduced a small magnetic sphere into the intraocular cavity of experimental animals. The sphere was subsequently maneuvered gently over the retina to unfold and reposition it with a small external permanent magnet probe. We used 68 enucleated canine eyes; eight eyes were operated in vivo and then examined microscopically. Retinal damage was caused by friction and excessive pressure when we used external magnets that were too strong or spheres that were too large. When small intraocular magnetic spheres coated with silicone or teflon or encased in a hollow oversize epoxy sphere were used the damage to the retina was minimal, or absent. We suggest using this same technique to treat retinal tumors through the introduction of radioactive material or antitumoral drugs. The intraocular magnetic sphere of this type would be left inside the eye in contact with the lesion for an extended period (seven days to three months) by suturing a small magnet to the sclera over the lesion.

Animals

Relationship between mianserin plasma levels and antidepressant effect in a double-blind trial comparing a single night-time and divided daily dose regimens.

1. Twenty-six in-patients and 24 out-patients suffering from moderate or severe primary depressive illness were randomly allocated to either a single night-time dose of mianserin 60 mg or a three times daily regimen in a double-blind controlled trial. 2. There was no significant difference in antidepressant effect between the two dosage regimens in either patient group measured using Hamilton Rating Scale (HRS), the Beck Self-Rating Inventory (BSRI) and the new Montgomery and Asberg Depression Scale (MADS). 3. A significant negative correlation (-0.36 P less than 0.05) was found between plasma levels and clinical response using the MADS. A trend for patients with low levels to do worse was also observed suggesting a curvilinear relationship. A highly significant poorer clinical response in patients with levels above 70 microgram/1 was observed using the MADS (t = 3.33, P less than 0.005). This was also seen with the HRS (t = 2.42, P less than 0.02). 4. A significant correlation (r = 0.29, P less than 0.05) with age is reported, and a highly significant increased variability (F = 7.07, P less than 0.001) of mianserin plasma levels in patients over 55 was demonstrated.

Adult

Dosage adjustment from simple nortriptyline spot level predictor tests in depressed patients.

20 routine patients with endogenous depression were investigated in a kinetic and 4 week treatment study. Steady-state plasma nortriptyline concentrations above 200 microgram/L were associated with a highly significant poorer therapeutic outcome. The correlations between the 24, 48 and 72 hour concentrations and steady-state concentration were very good (r = 0.81, 0.97, 0.94; p less than 0.0001) and better than the correlation between half-life and steady-state (r = 0.65; p less than 0.01). The Spearman rank correlations (Rs) between amelioration of depression measured by the Hamilton Rating Scale (HRS) and the 24, 48 and 72 hour concentrations were highly significant (Rs = 0.74, 0.79, 0.79; p less than 0.001) but for half-life (Rs = 0.33) the correlation was not significant. The single 48 hour plasma nortriptyline concentration following a single oral dose is recommended as a reliable simplified monitoring test suitable for a busy clinic. The test is useful for dosage adjustment to maximise antidepressant action and minimise toxicity. A tentative dosage adjustment schedule for individualising antidepressant treatment with nortriptyline based on the 48 hour or the 24 hour plasma concentration is proposed.

Clinical Trials as Topic

Mianserin plasma levels and differential clinical response in endogenous and reactive depression.

Fifty patients with moderate to severe primary depression were treated in equal groups of inpatients and outpatients with a constant dose of 60 mg. of mianserin daily for four weeks in a double blind placebo controlled trial with either a three times daily dosage regime or a single nightly dose. There was no difference in apparent compliance, side effects or therapeutic effect in either day-time or night-time dosage regimes. Patients developing high plasma levels of mianserin (greater than 70 microgram/l) were associated with a highly significantly poorer therapeutic outcome. Patients identified as endogenous depression demonstrated a significant negative correlation between plasma levels of mianserin and therapeutic response measured as an amelioration of either the Hamilton Rating Scale scores (r = --0.48) or on a new depression scale by Montgomery and Asberg (r = --0.51) with high levels associated with poor response. There was a significant correlation (r = 0.66) between mianserin plasma levels and age in endogenous depression. In those patients identified as suffering from reactive depression, no significant relationship could be seen between plasma levels and therapeutic response or with age. These findings support the view that the relationship between mianserin plasma levels and clinical response is more likely to be demonstrated in endogenous depression.

Adjustment Disorders