Steven C. Dilsaver

Lifetime Rates of Suicide Attempts among Subjects with Bipolar and Unipolar Disorders Relative to Subjects with Other Axis I Disorders

The lifetime rate of suicide attempts among subjects in the Epidemiologic Catchment Area database with bipolar disorder, unipolar disorder, and any other DSM-III-defined Axis I disorder were determined. The latter constituted a control or reference group. The lifetime rates of suicide attempts of persons in these diagnostic groups were 29.2%, 15.9%, and 4.2%, respectively. Multivariate logistic regression analysis was used to calculate the odds ratio of subjects within a diagnostic group having a history of a suicide attempt relative to subjects in a second group. The odds ratio of subjects with bipolar disorder having a history of a suicide attempt relative to subjects in the control group was 6.2 (df 1, x(2) = 5347.2, p < .0001). The odds ratio of subjects with unipolar disorder having a history of a suicide attempt relative to subjects in the control group was 3.1 (df = 1, x(2) = 4785.2, p < .0001). The odds ratio of subjects with bipolar disorder having a history of a suicide attempt relative to unipolar subjects was 2.0 (df = 1, x(2) = 697.9, p < .0001). Bipolar disorder has a strong relationship to a history of suicide attempts relative to unipolar disorder and other Axis I disorders.

Suicidality, panic disorder and psychosis in bipolar depression, depressive-mania and pure-mania

This study was undertaken to assess links between suicidality, panic disorder, psychosis, bipolar depression, depressive-mania and pure-mania. The subjects are a consecutive series of 129 persons with bipolar disorder who were admitted to a university teaching hospital; 53 had bipolar depression, 32 had depressive-mania and 44 had pure-mania. They met the Research Diagnostic Criteria (RDC) for major depressive disorder (bipolar depression), primary mania (pure-mania) or both disorders (depressive-mania) at entry into the study. Suicidality, intra-episode panic disorder (IEPD) and psychotic features were ascertained using structured interviews. Sources of data included a routine clinical interview, serial clinical assessments, the Schedule for Affective Disorders and Schizophrenia (SADS), the Structured Clinical Interview for DSM-III-R and reviews of charts. Multivariate logistic regression analysis was used to determine the strength of the relationships between suicidality, IEPD, psychotic features and the phase of illness. The rates of suicidality (79.3%, 56.3% and 2.3%), IEPD (62.3%, 62.5% and 2.3%) and psychotic features (52.8%, 96.9% and 88.6%) differed significantly between the groups with bipolar depression, depressive-mania and pure-mania. Subjects with bipolar depression and depressive-mania resembled one another with respect to the severity, but not rate of suicidality. They had identical rates of IEPD. Subjects with bipolar depression had a higher probability of being suicidal and a lower probability of being psychotic than persons with either subtype of mania. Pure-mania was distinguished by low rates of suicidality and IEPD. The authors describe directions for prospective studies of the relationships between phase of illness and phenomena in groups of bipolar persons.

Treatment of bipolar depression with carbamazepine: Results of an open study

Bipolar disorder (BPD) is a serious, potentially lethal disease afflicting 1.2% of the adults in the United States (Weissman et al 1988). The rate of illness increases greatly if variants such as cyclothymia and pseudounipolar disorder are included in estimates. Morbidity and early mortality stem from multiple sources; 18.9% of the deaths of 9389 bipolar patients were due to suicide (Goodwin and Jamison 1990 pp 228-230). Substance abuse is an important factor (Regier et al 1990). The lifetime rate of the abuse of or dependence upon alcohol and/or other drugs is 61% (Goodwin and Jamison 1990 pp 210-226). Antidepressants may have pernicious effects on persons with BPD. They may induce rapid cycling (Wehr and Goodwin 1989), mania (Wehr and Goodwin 1989; Angst 1985), or mixed states (Dilsaver and Swarm 1995). Despite deficiencies of existing regimens for BPD and its epidemiological significance, minimal effort is devoted to the development of new strategies for its treatment. Goodwin and Jamison (1990) provide a detailed history of the treatment of BPD. Only recent contributions will be reviewed here. Lithium (Goodwin et al 1969; Wehr and Goodwin 1989), bupropion (Haykel and Akiskal 1989), and tranylcypromine (Himmeloch et al 1991) are alternative treatments. Bupropion may be useful in the treatment of rapidly cycling patients (Haykel and Akiska 1989) and persons with depressive mania

Antidepressant Withdrawal Syndrome

SummaryWithdrawal from tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs) and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) can produce somatic and psychological distress. Influenza-like syndromes, gastrointestinal adverse effects, arrhythmias, anxiety, sleep disturbances, movement disorders, mania or hypomania, panic attacks and delirium may follow antidepressant withdrawal. At present, the aetiology of withdrawal symptoms is not fully known.Withdrawal phenomena are usually prevented by gradually reducing the total daily dosage of the drug in question rather than abruptly discontinuing it. Antimuscarinic agents can be prescribed in order to alleviate the symptoms produced by the withdrawal of TCAs and MAOIs. To date, no drugs have been shown to be useful in the treatment of SSRI-associated withdrawal symptoms. The withdrawal syndrome associated with MAOIs may constitute a medical emergency.

Measurement of temperature in the rat by rectal probe and telemetry yields compatible results

The change in body temperature of the rat is commonly measured using biotelemetry or the rectal probe. The authors report that the two methods yield qualitatively similar but quantitatively different results in two experiments. In Experiment 1, both methods detected a salicylate-affected reduction in handling-induced hyperthermia. In Experiment 2, both methods were useful in detecting the hypothermia induced by the muscarinic agonist oxotremorine. In both Experiments 1 and 2, measurements of baseline temperature were higher when measured with the rectal probe. Baseline temperature is measured with biotelemetry prior to handling animals, whereas the act of measuring baseline temperature with the rectal probe necessitates handling. The investigators hypothesized that a rise in baseline temperature produced by handling at least partially accounts for the greater hypothermic response obtained in Experiment 2 using measurements obtained with the rectal probe. In Experiment 3, baseline temperature was measured with biotelemetry after animals were handled. Handling produced an increase in baseline temperature. The hypothermic response to oxotremorine was increased when the higher posthandling baseline temperature was used to calculate the hypothermic response of animals. The authors conclude that differences in baseline temperature and hypothermic response obtained with the two methods are related to an effect of handling.

Secondary social phobia in patients with major depression

Nineteen of 42 (45.2%) patients were socially phobic when and only when depressed. Each of these patients met diagnostic criteria for primary depression (Research Diagnostic Criteria) and major depression (DSM-III-R). Every subject had three or more distinct episodes of depression. Eight of the 9 men (88.9%) and 11 of the 33 women (33.3%) were socially phobic when depressed (p = 0.004). Patients with recurrent wintertime episodes of major depression (p = 0.036) and a past history of alcohol or drug abuse were more likely to be socially phobic (p = 0.0001). The authors suggest the 19 socially phobic patients with primary depression should be regarded as having secondary social phobia. Secondary social phobia may be an important source of comorbidity in patients with primary depression.

Chronic forced swim stress produces subsensitivity to nicotine

Twice daily injections of saline reduce the thermic response to nicotine in the rat. The authors hypothesized that this was due to the stress of twice-daily handling and injection. However, the injection of saline is not a classic stressor. The hypothesis that stress blunts thermic responsiveness to nicotine was, therefore, tested using a classic form of chronic inescapable stress. Rats (n = 12) were subjected to a 14-day, twice daily course of inescapable cold water swim stress using a repeated measures design. Thermic responsiveness of nicotine was measured at baseline and every 7 days thereafter for 49 days. The mean response to nicotine (1.0 mg/kg IP) differed significantly across time, F(7,88) = 10.6, p less than 0.0001. Mean thermic responsiveness (+/- SEM) decreased from -0.75 +/- 0.09 at baseline to -0.41 +/- 0.18 degrees C (54.7% of baseline) following 14 days of forced swim stress. This change was not significant. However, the thermic response to nicotine was -0.14 +/- 0.13 degrees C (p less than 0.05), +0.55 +/- 0.12 degrees C (p less than 0.05), and +0.04 +/- 0.11 degrees C (p less than 0.05) 7, 14, and 21 days following the discontinuation of forced swim stress. The mean response did not differ from baseline 28 days following the last session of forced swim stress. The data suggest that in the recovery phase the animals ceased to be sensitive to nicotine. These findings support the hypothesis that a chronic stressor can produce subsensitivity to nicotine.

Mania: gender, transmitter function, and response to treatment

Noradrenergic and GABA systems may be involved in mania, but there is little information about relationships between the function of these systems and response to specific antimanic treatments. We investigated relationships between indices of catecholamine or GABA system function, pretreatment mania severity and antimanic response to divalproex, lithium, or placebo. Plasma GABA and urinary excretion of catecholamine metabolites were measured before randomization to lithium, divalproex or placebo in patients hospitalized for manic episodes. Severity of mania was evaluated using the Manic Syndrome, Behavior and Ideation and Mania Rating Scale scores from the SADS-C. Multiple regression analysis showed that pretreatment plasma GABA was related to severity of manic symptoms. This relationship seemed stronger in women. Multiple regression analysis showed that pretreatment levels of urinary MHPG correlated with improvement in manic syndrome scores. These data suggest that GABA and norepinephrine may be related to different aspects of the manic state and to its pharmacologic sensitivity.

Chronic treatment with ethanol alters the physiological action of nicotine

1. Ethanol decreases the release of acetylcholine through effects on presynaptic neurons at both muscarinic and nicotinic junctions. 2. Blockade of the release of acetylcholine should produce denervation supersensitivity at both muscarinic and nicotinic cholinergic junctions. 3. Chronic but not acute treatment with ethanol produces supersensitivity to the hypothermic effects of a muscarinic agonist in the rat. 4. The authors now report that chronic treatment with orally administered ethanol blunts (rather than enhances) the hypothermic response to nicotine in the rat. 5. This could have major public health implications. 6. Smoking and the use of ethanol containing beverages positively covary. 7. Ethanol induced reduction in sensitivity to nicotine suggests that the heavy consumption of ethanol may necessitate that one drink more than otherwise in order to obtain the desired effects of nicotine.

Chronic treatment with valproate decreases the hypothermic response to clonidine

Treatment with lithium (the prototype of an antimanic agent) attenuates responsiveness to the alpha 2-agonist clonidine in animal models. Valproate is now used to treat mania. The effect of treatment with this drug on responses mediated by an alpha 2-agonist have yet to be reported. The authors assessed the effect of a 14-day course of orally administered valproate on the rats hypothermic response to clonidine. Treatment with valproate decreased this response.