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Differential features between bipolar I and bipolar II disorder.

Although bipolar II disorder is generally viewed as a mild form of classic manic-depressive illness, recent investigations suggest that it could be a valid diagnostic category different from bipolar I in genetic, biological, clinical, and pharmacological aspects. Twenty-two patients fulfilling Research Diagnostic Criteria for the diagnosis of bipolar II disorder and 38 bipolar I patients were evaluated with the Schedule for Affective Disorders and Schizophrenia by two independent interviewers and compared. Bipolar II patients had significantly more previous episodes (P = .001), including both depressive (P = .003) and hypomanic (P = .006) switches, but had been hospitalized (P = .001) and presented psychotic symptoms (P < .001) less frequently. These results suggest that bipolar II disorder is less severe than bipolar I with regard to symptom intensity, but is more severe with respect to episode frequency.

A long-term prospective study on the outcome of bipolar patients treated with long-acting injectable risperidone

Background: Risperidone is the first atypical antipsychotic to become available in a long-acting, injectable formulation. This is the first prospective study to assess the effectiveness of long-acting risperidone in a cohort of bipolar patients. Methods: Twenty-nine DSM-IV acutely manic bipolar inpatients with a history of poor or partial adherence to medication entered the mirror-design observational study. They received naturalistic treatment for a manic episode plus long-acting, injectable risperidone for a mean period of 2 years. The following measures were used to assess the effectiveness of risperidone: the number of hospitalizations, the number of manic, mixed, and depressive episodes leading to hospitalization, the mean duration of hospitalizations, time to relapse, treatment adherence, aggression and suicide attempts. The Clinical Global Impressions (CGI) was used for clinical relevance as well. Results: During the follow-up, there was a significant decrease in the number of hospitalizations per patient (Z−2.72 P<0.006), in the number of manic or mixed episodes leading to hospitalization (Z−2.68 P<0.007) but not in the hospitalizations due to depressive episodes, a decrease in the average length of hospitalization per patient (Z−3.27 P<0.001), a significant increase in the time to any new episode (first relapse) (Z−3.28, P<0.001), and significant improvements in treatment adherence (P<0.0001) and hetero-aggressive episodes (P<0.0001), but not suicide attempts (P=NS). At study endpoint 14 patients (48%) were very much improved according to the CGI. Discussion: This observational long-term study provides support to long-acting injectable risperidone being effective for the maintenance treatment of mania and improving treatment adherence, reducing relapses and re-hospitalization rates.

Serious suicide attempts in affective patients

A retrospective study was carried out including all patients who in the previous 6 years had required admission to our hospital for medical or surgical reasons following attempted suicide (n = 257). Those diagnosed as having affective disorder (n = 96), according to DSM-IIIR criteria, were compared with the other non-affective suicide attempters (n = 161). Affective patients were significantly different in that they were older, more often women, married or widowed, usually used non-violent methods, made more serious attempts and presented a higher incidence of concomitant physical illness. Affective patients with a history of previous attempts were more likely to be recurrent unipolar depressives or first episode unipolars with a concurrent diagnosis of personality disorder. Most of the depressed patients made the attempt within the first 12 months of the episode. Patients who attempted suicide in the first 12 months of the depression were more likely to use non-violent methods and to receive a diagnosis of bipolar or unipolar recurrent disorder.

Prediction of depressive relapse in remitted bipolar patients using corticotrophin‐releasing hormone challenge test

Abnormalities in corticotrophin (ACTH) and Cortisol levels before and after corticotrophin‐releasing hormone (CRH) stimulation have been reported in depressed bipolar patients. The ACTH and free Cortisol response to the injection of 100 ug of synthetic human CRH and plasma cortisol‐binding globulin (CBG) levels were measured in 42 lithium‐treated patients suffering from RDC bipolar‐I disorder in remission, and in 21 age‐ and sex‐matched control subjects. A 1‐year follow‐up was conducted in order to assess any possible relationship between outcome and the hormonal response. Bipolar patients showed higher baseline and peak ACTH concentrations than controls. A lower net area under the ACTH concentration curve after CRH stimulation predicted depressive relapse within 6 months by multiple regression analysis. The CRH challenge test could be a potentially good predictor of depressive relapse in remitted bipolar patients.

Suicide attempts of high medical seriousness in schizophrenic patients.

A retrospective study was conducted that included all patients who in the previous 6 years had required admission to our hospital for medical reasons following attempted suicide (N = 253). Those diagnosed as schizophrenic (n = 43) in accordance with DSM-III-R criteria were compared with the other nonschizophrenic suicide attempters. Schizophrenic patients were significantly different in that they were younger and generally unmarried, usually used violent methods, made more attempts while in a psychiatric center, and presented a lower incidence of concurrent organic illness than the nonschizophrenics; almost all of them were chronic. A large majority (80%) showed delusional and hallucinatory symptoms at the time of the attempt. In contrast, depressive symptoms were noted in an appreciably lower percentage of subjects than that in other studies of suicidal behavior in schizophrenics.

Adjunctive gabapentin treatment of bipolar disorder.

INTRODUCTION The aim of this study was to analyze the effectiveness of gabapentin administration to bipolar patients who had an incomplete response to other mood stabilizers. SUBJECTS AND METHODS Twenty-two RDC bipolar 1 and II patients were assessed by means of the SADS and entered if they gave their consent to participate. All them had suffered from frequent relapses, subsyndromal features (mostly depressive) and incomplete response to other drugs. They all received open-label increasing doses of gabapentin until clinical response. The patients were assessed through the CGI-BP and a specific questionnaire at baseline and at 12 weeks of follow-up. RESULTS Six out of the 22 patients dropped out for various reasons (four because of relapse, one because of side effects and one more because of poor compliance). Eight of the 16 patients that completed the 12-week follow-up showed at least two stages of improvement in the CGI. Using the last observation-carried forward analysis, the improvement was statistically significant for the depression subscale, and apparently related to social functioning, irritability and anxiety. Only one patient dropped out because of intolerance (mild rash). The mean dose of gabapentin was 1,310 mg/day. CONCLUSION Gabapentin may be a useful drug for the add-on treatment of bipolar patients with poor response to other mood stabilizers. Gabapentin may improve depressive residual symptoms such as irritability, social withdrawal or anxiety. These results should be confirmed in randomized clinical trials.

Recurrent brief depression successfully treated with lithium

BACKGROUND The diagnostic criteria for RBD requires the presence of at least five out of nine depressive symptoms analogous to the symptoms of major depression, yet a duration of less than two weeks, a recurrence of at least 12 times a year, and the evidence of impairment in occupational or other important areas of functioning. The lack of a successful treatment represents one of the main challenges of this disorder. The therapeutic value of lithium in RBD has been suggested by Montgomery, but the specific efficacy of this agent has not been tested yet in the case of patients with recurrent brief depressive disorder. METHODS We report on a 38-year-old man who presented a 10-month history of sudden depressive episodes, with monthly recurrences lasting 2-4 days, prior to our first assessment. RESULTS The patient was treated with clomipramine, with complete remission of the depressive episode after three days. Nevertheless, in spite of maintaining the treatment, he presented a new episode one month later and two episodes the month after. Since then, lithium therapy was added and during the last 13 months he has remained euthymic, without any recurrence of depressive symptoms. Lithium treatment has been maintained and clomipramine treatment was gradually tapered because of the complaints of impotence, dry mouth, and dizziness. CONCLUSIONS The absence of recurrences since lithium treatment was started (during the last 13 months, and especially during the last 10 months, where lithium has been the only treatment), suggests a prophylactic effect of this agent on RBD. Lithiums mechanism of action in preventing depressive recurrences might play a major role in the therapeutic approach of RBD, especially since recurrence (but not the duration of the symptoms) is the main feature that defines the severity of this disorder.

Alpha-1-acid glycoprotein in major depressive disorder: Relationships to severity, response to treatment and imipramine plasma levels

Abstract Background: Increased plasma levels of alpha-1-acid glycoprotein (AGP) were reported in major depressive disorder. However, the relationship between AGP levels, severity of depression, treatment response and antidepressant levels are still unclear. Methods: Plasma AGP levels were measured in 36 subjects with major depressive disorder before and after a 6-week treatment with imipramine and in 30 controls. Free imipramine plasma levels of depressed patients were measured at 6 weeks. Comparative analysis between depressed patients and controls, between non-responders ( N =12) and responders ( N =24), and between severely depressed patients ( N =14) and moderately depressed patients ( N =22) were made. Results: Depressed patients had significantly higher mean values of AGP than control subjects. Imipramine non-responders and specially severely depressed patients had significantly greater increases of AGP levels during treatment than other depressed subgroups. There was no correlation between baseline AGP levels and severity of depression or free imipramine levels. Limitations: The most significant limitations of this study are the small sample size and the fact that all the subjects were out-patients. Results should not be generalized to in-patient populations. Conclusions: Depressed patients showed high baseline concentrations of AGP. AGP levels did not predict either free imipramine plasma levels or differential response after 6 weeks of treatment with imipramine. A greater increase of AGP during treatment was associated with severity of depression and treatment non-response. Clinical implications: The relationship between high plasma levels of AGP, severity of depression and lack of treatment response is clarified. The influence of imipramine levels is minimized.

Serious Suicide Attempts in the Elderly

A retrospective study was carried out including all those patients who, over the last 6 years (n = 257), required admission to our hospital for medical or surgical reasons following attempted suicide. The authors examined a series of clinical and demographic variables. Thirty-eight patients over 65 years of age were compared with 120 patients aged between 30 and 64 years and 99 aged under 30 years. When compared with the other two groups, a significantly higher proportion of elderly patients were widowed and showed affective disorders and concurrent physical illness.

Making sense of DSM-5 mania with depressive features

Objective: The assessment of the depressive component during mania has become critical for the accurate diagnosis of mixed states, which were defined very narrowly in the past classification systems before Diagnostic and Statistical Manual of Mental Disorders (5th ed.). The aim of this study was to compare socio-demographic, clinical and therapeutic characteristics, as well as clinical and functional outcomes, between manic patients with and without mixed features to validate the relevance of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) mixed specifier. Methods: This is a subanalysis of a multicentre naturalistic study MANía Aguda y COnsumo de Recursos (acute mania and health resource consumption [MANACOR]) on the burden of mania in bipolar patients from four hospitals in Catalonia (Spain). The sample consisted of 169 adult patients presenting a manic episode and systematically assessed during a 6-month period. Results: A total of 27% (n = 46/169) of manic patients showed mixed features. Total number of episodes (p = 0.027), particularly depressive and mixed, was greater in manic patients with mixed features, as well as depressive onset (p = 0.018), suicide ideation (p = 0.036), rapid cycling (p = 0.035) and personality disorders (p = 0.071). In contrast, a higher percentage of pure manic subjects were inpatients (p = 0.035), started the illness with mania (p = 0.018) and showed family history of bipolar disorder (p = 0.037), congruent psychotic symptoms (p = 0.001) and cannabis use (p = 0.006). At baseline, pure manic patients received more risperidone (p = 0.028), while mixed patients received more valproate (p = 0.049) and antidepressants (p = 0.005). No differences were found in syndromic recovery at the end of the study. However, depressive change was higher in the mixed group (p = 0.010), while manic change was higher in the pure manic group (p = 0.029). At the end of follow-up, the group with mixed features showed a significant trend towards higher psychosocial dysfunction. Conclusion: A total of 27% of manic patients showed mixed features. Groups differed regarding clinical characteristics, course of illness, psychosocial functioning, prescribed treatment and symptom progress. Depressive symptoms in mania should be routinely assessed and considered to guide treatment.