Emmanuel Persad

Comorbidity of obsessive compulsive disorder in bipolar disorder

The comorbidity of OCD and bipolar disorder has not been systematically examined. Therefore, we determined the frequency of patients meeting DSM-III criteria for OCD syndrome in a sample of 149 inpatients with DSM-III major affective disorder who had received a clinically reviewed structured diagnostic interview. The frequency of OCD syndrome was not significantly different between subjects with major depression (35.2%, n = 105) and bipolar disorder (35.1%, n = 37). This suggests that OCD is equally common in bipolar as in unipolar patients.

A comparison of haloperidol, lithium carbonate and their combination in the treatment of mania

Previous investigations of the treatment of mania have resulted in uncertainty about the efficacy of lithium versus a neuroleptic. In addition there have been reports of toxicity with a haloperidol--lithium combination. In order to determine the comparative efficacy of lithium vs haloperidol vs a combination of haloperidol--lithium, we studied 21 severely ill manic patients who all met rigorous criteria for bipolar illness and who required in hospital treatment. Subjects were randomly assigned to 3 groups: (A) Lithium plus placebo (B) Placebo plus haloperidol and (C) Lithium plus haloperidol. The study was conducted in double blind fashion for 3 weeks with the dosages of the medications varied according to clinical response or untoward effects. Subjects on haloperidol and placebo or the haloperidol--lithium combination were significantly improved after 7 days in comparison to the lithium-treated group. Groups B and C did not differ from each other, either in degree of improvement or in side effects. Inspite of the relatively small sample size the results suggest (1) that haloperidol is superior to lithium for treating severely ill acute mania and (2) that while a haloperidol--lithium combination does not result in a significant increase in side effects, it is not superior to haloperidol alone.

A closer look at inpatient suicide

BACKGROUND We examined the risk factors for suicide among inpatients in an Ontario provincial psychiatric hospital. METHODS Forty-four inpatients who had committed suicide during their hospital stay from 1969 to 1995 were compared with a group of inpatient controls matched for sex, age and date of admission. The diagnosis for each patient was reviewed by the authors. RESULTS Suicide victims were more likely to have had a mood disorder, family history of psychiatric problems, mention of suicide risk in chart notes and a previous suicide attempt. Two findings necessitated further scrutiny: The most common diagnosis among inpatients who committed suicide in this study was a mood disorder and not schizophrenia as previously reported. A large proportion of patients (24) had experienced a rapidly fluctuating clinical course prior to the time of suicide. CONCLUSIONS The implications of these findings, including the possible role of antidepressants in the induction of cycling prior to suicide, are discussed.

Treatment of rapid cycling bipolar disorder with combination therapy of valproate and lithium.

Over the past two decades there has been a great deal of interest in the use of anticonvulsants to treat a variety of primary psychiatric disorders. Valproate, one such anticonvulsant, has been found to be effective in the treatment of acute mania, mixed states and rapid cycling disorders. This paper presents the results of an open study with combination therapy of valproate and lithium in a series of nine patients (mean age = 50 years). These patients had previously been treated with various psychotropic agents, including a combination of carbamazepine and lithium. All but one patient showed marked or moderate improvement in their condition. Of particular interest was the observation that in three patients there was evidence of augmentation between valproate and lithium during the depressed phase of their illness. There was significant improvement in their depression within 24 to 48 hours of the addition of lithium to valproate. The combination therapy was very well-tolerated. It is concluded that valproate and lithium combination therapy provides a safe and effective alternative for the treatment of rapid cycling variant of bipolar illness.

EVIDENCE FOR HOMOGENEITY OF MAJOR DEPRESSION AND BIPOLAR AFFECTIVE DISORDER

This study compared the morbidity risk for affective disorder in relatives of probands who had bipolar (BP) or major depression (UP). Other risk factors were also evaluated. 112 consecutively admitted inpatients yielded 621 relatives with diagnostic information based on either the Renard diagnostic interview, hospital records or information from at least two reliable relatives using the Feighner diagnostic criteria. Similar age corrected morbid risk estimates were found for family members of UP and BP probands of 0.243 and 0.246. There was a 50% increase in morbidity risk for women in all three generations but no relationship to the diagnosis of the proband. A proportional hazards (life table) analysis demonstrated that probands with onset prior to age 40 had relatives with younger onset and higher risk. None of the analyses, including logistic regression and proportional hazards, differentiated UP from BP illness.

The nonlinear kinetics of desipramine and 2‐hydroxydesipramine in plasma

Plasma levels of desipramine (DMI) and the unconjugated form of its principal metabolite 2‐hydroxydesipramine (OH‐D) were measured under steady‐state conditions in nine depressed inpatients during treatment with 75 mg DMI every 12 hr and after at least 1 wk of an increased dose of DMI (after steady state). When DMI dosage was raised after an initial steady state had been reached, the rise in plasma DMI level was proportionately greater than the increase in dosage, suggesting saturation of DMI elimination pathways. Levels of OH‐D rose in proportion to dose, suggesting that saturation of DMI elimination by 2‐hydroxylation could not explain DMI plasma level changes. In contrast, there were no dose‐dependent effects on the disposition of amitriptyline or its metabolite nortriptyline in subjects receiving the same amitriptyline dose.

Effect of Pregnancy on Three Patients with Bipolar Disorder

Case histories of three bipolar II disorder patients who had periods of sustained euthymia during all their pregnancies are described. The clinical and research implications of these observations are discussed.

Confirmation of the relationship of HLA (chromosome 6) genes to depression and manic depression II. The Ontario follow-up and analysis of 117 kindreds

HLA typing was conducted on 577 family members of 86 families having at least two first‐degree family members with a lifetime history of major depression or bipolar disorder. The results were combined with a follow‐up study of 10 Newfoundland kindreds and with the data obtained from our previous studies, giving a total cohort of 117 families of diverse ethnic and geographic origin. There was increased sharing of HLA haplotypes, as compared with random expectation, over all possible pairwise comparisons both in the follow‐up studies (P < 0.025) and in the total data (P < 0.01). The increase in HLA haplotype sharing over random expectation was greater if comparisons within heavily loaded sibships (by prior convention, sibships with three or more affected siblings) were omitted from the analysis (P < 0.002). There was also non‐random transmission of HLA haplotypes in 50 families selected for a low‐load, unaffected parent (P < 0.005). Thus, we conclude that genes in the HLA region of chromosome 6 constitute one of the elements in the multifactorial etiology of affective disorder. This conclusion does not depend on any assumption concerning genetic heterogeneity or epistasis or on specific modes of transmission, penetrance values or linkage distances. In addition, the data suggest that chromosome 6 region genes may have a different effect in unipolar and bipolar illness.

A comparison of comorbid patterns in treatment-resistant unipolar and bipolar depression.

Objective To examine the occurrence of concomitant psychiatric disorders in patients with treatment-resistant unipolar and bipolar depression. Method Forty-nine patients participated as subjects. Twenty-four (49%) had unipolar depression and 25 (51%) had bipolar depression using DSM-III-R criteria. Structured clinical interviews were conducted with all patients. Chart reviews and interviews with family members were also carried out. Information relating to both current and lifetime diagnoses was obtained. Results Of the entire sample, 75.5% were found to have at least one other Axis I diagnosis and 46.9% had at least two additional Axis I diagnoses. The unipolar group had significantly more current comorbid diagnoses. When type of diagnoses was examined, unipolar patients had significantly more anxiety diagnoses at the time of the index episode, and over their entire lifetime. Bipolar patients had significantly more lifetime substance abuse diagnoses. Conclusions Axis I comorbidity appears to be differentially associated with treatment resistance in unipolar and bipolar depression.

The phenomenon of rapid cycling in bipolar mood disorders : a review

Objective: To review the various pharmacological and nonpharmacological factors associated with the induction of rapid cycling in bipolar mood disorder, and to introduce the idea that parturition may also have a role. Factors known to contribute to bipolar mood disorder rapid cycling include antidepressant agents, female gender and middle age. Currently, there is evidence that hypothyroidism may also play a role. Method: A critical review of the literature was undertaken. Conclusion: Caution should be exercised in the use of antidepressants in patients with bipolar mood disorders.