Víctor Navarro

Relapse of major depression after complete and partial remission during a 2-year follow-up

BACKGROUND Rates of remission and relapse were studied over more than 2 years in a sample of Spanish outpatients with DSM-III-R criteria of unipolar major depressive episodes. METHODS Patients were treated following standardised pharmacological protocols at our centre. In the first visit, the structured clinical interview for DSM-III-R (SCID) was used. The following visits were held monthly. Phases of evolution were recorded using the Hamilton Depression Rating Scale (HDRS), applying the Frank criteria. RESULTS A significantly greater proportion of relapse was observed in the partial remission group compared to the complete remission one. The rate of relapses for patients in complete remission was 15.18%, while for patients in partial remission was 67.61%. Partial remission was significantly associated with relapses. LIMITATIONS The short duration of the study and the decreasing sample size during the follow-up. CONCLUSIONS Partial remission after a depressive episode seems to be strongly associated with relapses. Moreover, this clinical factor could by itself fully predict short-term relapses. CLINICAL RELEVANCE The study shows the importance of reaching complete remission to decrease the rate of short-term relapses.

Executive function needs to be targeted to improve social functioning with Cognitive Remediation Therapy (CRT) in schizophrenia.

While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established, the relationship between cognitive and functional change in the context of treatments is far from clear. The current paper tries to identify which cognitive changes lead to improvements in daily functioning among persons with chronic schizophrenia who had current negative symptoms and evidenced neuropsychological impairments. In a previous work, Cognitive Remediation Therapy (CRT) was compared with a control therapy, involving similar length of therapist contact but different targets. At the end of treatment, CRT conferred a benefit to people with schizophrenia in cognition and functioning [Schizophrenia Research, 87 (2006) 323-331]. Subsequently, analyses of covariance (ANCOVA) were conducted with baseline and cognitive change scores as covariates to test whether cognitive change predicted change in functioning. Additionally, statistical tests to establish the mediation path with significant variables were performed. Although verbal memory, but not executive functioning, was associated with functioning at baseline, it was the improvement in executive functioning that predicted improved daily functioning. Verbal memory played a mediator role in the change process. Consequently, in order to improve daily functioning with CRT, executive function still needs to be targeted in despite of multiple cognitive impairments being present.

Citalopram versus nortriptyline in late-life depression : a 12-week randomized single-blind study

Objective: The aim of this single‐blind study was to examine the efficacy and tolerability of citalopram compared to nortriptyline in moderate to severe major depressive patients aged 60 years or over.

Normalization of frontal cerebral perfusion in remitted elderly major depression: a 12-month follow-up SPECT study.

We examined global and regional cerebral blood flow abnormalities in a group of unmedicated nondemented elderly late-onset unipolar major depressed patients in acute depression and in remission (after a 12-month follow-up period). 35 somatic treatment remitter patients over the age of 60 years and 20 sex-, age-, and vascular risk factor-matched healthy controls were imaged with single photon emission computed tomography, using technetium-99m hexamethylpropylene amine oxime as a tracer. In depression, the depressed group had significantly lower uptake in the left anterior frontal region than the control group. In remission, the left frontal cerebral perfusion abnormalities disappeared, and there were no significant differences in uptake between controls and patients. No significant correlations were found between baseline clinical characteristics of patients and their regional cerebral perfusion at baseline or after a 12-month follow-up. These findings are consistent with the hypothesis that certain neuroanatomic regions of the central nervous system may be functionally and reversibly involved in unipolar major depression, particularly in the late-onset subgroup.

Continuation/Maintenance Treatment with Nortriptyline Versus Combined Nortriptyline and ECT in Late-Life Psychotic Depression : A Two-Year Randomized Study

OBJECTIVE The identification of effective continuation and maintenance strategies for elderly patients with psychotic depression is a critical issue that has not been fully explored. The aim of this study was to assess the tolerability and efficacy of continuation/maintenance electroconvulsive therapy (ECT) in elderly patients with psychotic depression after acute ECT remission. METHODS The authors used a longitudinal, randomized, single-blind design to compare by survival analysis the 2-year outcome of two subgroups of elderly patients with psychotic unipolar depression who were ECT (plus nortriptyline) remitters. One group was treated with a continuation/maintenance nortriptyline regimen (N = 17) and the other with combined continuation/maintenance ECT plus nortriptyline (N = 16). RESULTS Over 2 years of treatment in elderly, psychotic, unipolar depressed ECT (plus nortriptyline) remitters, the mean survival time was significantly longer in the combined ECT plus nortriptyline subgroup than in the nortriptyline subgroup. No differences were observed between treatments with regard to tolerability. CONCLUSIONS This study supports the judicious use of combined continuation/maintenance ECT and antidepressant treatment in elderly patients with psychotic unipolar depression who are ECT remitters.

Single-blind comparison of venlafaxine and nortriptyline in elderly major depression

The objective of this single-blind study was to compare the efficacy and safety of venlafaxine extended-release and nortriptyline in elderly patients with moderate to severe major depression. In- and out-patients (N=68) with unipolar major depression were randomized to receive 6-month treatment with either nortriptyline or venlafaxine. Outcomes of the two groups were compared using measures including the Hamilton Depression Rating Scale (HDRS) and the Newcastle Scale. Side effects were assessed with the UKU side-effect rating scale. Of the 34 venlafaxine-treated patients, 22 were remitters, 7 were nonremitters, and 5 dropped out. The intent-to-treat remission rate was 71% (22 of 31). Of the 34 who received nortriptyline, 21 were remitters, 7 were nonremitters, and 6 dropped out. The intent-to-treat remission rate was 70% (21 of 30). These results suggest that the remission rate with a therapeutic plasma level of nortriptyline is similar to the remission rate with a standard dose of venlafaxine in this group of elderly major depressed patients. No significant differences were observed between dropout rates in the two groups, but autonomic side-effects were significantly more frequent for nortriptyline than for venlafaxine. These results confirm the efficacy and safety of venlafaxine extended-release for treating elderly major depression.

Frontal Cerebral Perfusion Dysfunction in Elderly Late-Onset Major Depression Assessed by 99MTC-HMPAO Spect

Baseline regional cerebral blood flow of thirty unmedicated late-onset unipolar major depressed patients over the age of 60 years and 20 sex-, age-, and vascular risk factor-matched healthy controls was imaged with single photon emission computed tomography, using technetium-99m hexamethylpropylene amine oxime as a tracer. To avoid errors of diagnosis--in particular, confusion between major depression and organic cognitive impairment--only treatment responders were included in the final sample. Statistically significant differences were observed in both left and right anterior frontal regions, with reduced uptake in depressed patients; these differences were more pronounced in the left hemisphere. Among patients, there was no correlation between regional cerebral blood flow and the severity of baseline symptoms. Our results support the hypothesis that certain neuroanatomic regions of the central nervous system may be functionally involved in elderly unipolar major depression, particularly in the late-onset subgroup.

Improving medication compliance in patients with depression: Use of orodispersible tablets

The treatment of major depressive disorder requires prolonged pharmacotherapy with antidepressants in order to resolve the current episode and reduce the risk for recurrence of depressive symptoms. Such prolonged therapy requires considerable commitment on the part of patients to take their medication as prescribed. Medication compliance is often poor among psychiatric patients, including those with major depressive disorder; this can result in poor long-term outcomes and, ultimately, treatment failure. The onus lies with the prescribing physician to support patients in complying with their medication regimen. Establishing and maintaining a supportive therapeutic relationship is an essential foundation for ensuring patient compliance. Difficulty in swallowing conventional tablets and capsules has emerged as an additional factor in medication noncompliance and has led to the development of alternative drug delivery strategies such as orodispersible tablets (ODTs). ODTs are associated with improved medication compliance compared with traditional tablet formulations. An ODT formulation of the antidepressant mirtazapine has been available since 2001 and an ODT formulation of escitalopram is currently in development. Such formulations offer convenient alternatives to traditional tablets and may support patient compliance with extended therapy. This review discusses practical methods of improving compliance in patients with depression with a particular focus on ODTs.

Residual symptoms in elderly major depression remitters

Objective:  To assess residual symptoms in severe geriatric major depression in remission, and to determine baseline clinical and sociodemographic predictors of residual symptoms in remitters.

Prothrombotic platelet phenotype in major depression: Downregulation by antidepressant treatment

BACKGROUND Serotonergic mechanisms have been suggested as a link between major depression and cardiovascular risk. We investigated the existence of a prothrombotic condition in depressed patients and its possible modulation during treatment with a selective serotonin-reuptake inhibitor (SSRI). METHODS Modifications in a series of biomarkers of platelet and coagulation activation were evaluated in blood from 19 patients with a major depression disorder (MDD) at the time of diagnosis, and at 8 and 24 weeks of treatment with escitalopram. Response of blood aliquots recirculated through a thrombogenic surface was assessed in a thrombosis model. Results were compared with those of 20 healthy-matched controls. RESULTS In comparison with controls, platelets from MDD patients showed elevated volumes (p<0.01), significantly enhanced aggregating response to arachidonic acid and augmented expression of GPIb, fibrinogen, factor V, and anionic phospholipids by flow cytometry (p<0.05). Clot firmness and procoagulant activity of platelet-associated tissue factor were also significantly elevated (p<0.05). Studies with circulating blood revealed increased fibrin formation in early diagnosed patients (71.1±9.5% vs. 45.8±5.3%; p<0.05 vs. controls). After 24 weeks of treatment with escitalopram, the majority of the alterations observed were normalized, except for a residual increased expression of GPIIbIIIa (p<0.05) and persistent alterations in thromboelatometic parameters. LIMITATIONS Despite the reduced number of followed-up patients our findings were consistent reaching statistical significance. CONCLUSIONS Our results reveal a prothrombotic phenotype in MDD patients. While continuous treatment with an SSRI downregulated the majority of the biomarkers analyzed, alterations in viscoelastic parameters of clot formation remained unaffected by the antidepressant treatment.