The Canadian Journal of Psychiatry

This systematic review examines the evidence and discusses the clinical relevance of lithium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research.

We searched the Medline computer database and the Cochrane Library for relevant original studies published in English from January 1966 to February 2003. The key words were as follows: lithium, augmentation strategies, lithium augmentation, major depression, refractory depression, treatment-resistant depression, neuroendocrinology, and serotonin.

Of 27 prospective clinical studies published since 1981, 10 were double-blind, placebo-controlled trials, 4 were randomized comparator trials, and 13 were open-label trials. Five of 9 acute-phase placebo-controlled trials demonstrated that lithium augmentation had substantial efficacy. In the acute-treatment trials, the average response rate in the lithium group was 45%, and in the placebo group, 18% (P < 0.001). One placebo-controlled trial showed the efficacy of lithium augmentation in the continuation-phase treatment. Summarizing the open and controlled data, approximately 50% of patients responded to lithium augmentation within 2 to 6 weeks. Animal studies offer robust evidence that lithium augmentation increases 5-HT neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways.

Augmentation of antidepressants with lithium is the best-documented augmentation therapy in the treatment of refractory depression. Emerging data from animal studies suggest that the 5-HTergic system is involved in the augmentatory effect of lithium.

To analyze new and reviewed findings to evaluate relations between treatment response and latency from onset of bipolar disorder (BD) to the start of mood-stabilizer prophylaxis.

We analyzed our own new data and added findings from research reports identified by computerized searching.

We found 11 relevant studies, involving 1485 adult patients diagnosed primarily with BD. Reported latency to prophylaxis averaged 9.6 years (SD 1.3), and follow-up in treatment averaged 5.4 years (SD 3.1). Greater illness intensity and shorter treatment latency were closely associated, resulting in a greater apparent reduction in morbidity with earlier treatment. However, this finding was not sustained after correction for pretreatment morbidity, and treatment latency did not predict morbidity during treatment. Therefore, assessments based on improvement with treatment, or without correction for pretreatment morbidity, can be misleading.

Available evidence does not support the proposal that delayed prophylaxis may limit response to prophylactic treatment in BD and related disorders.

Several papers have reported higher prevalence of diabetes mellitus (DM) type 2 in patients suffering from bipolar disorder (BD). The possible links between these 2 disorders include treatment, lifestyle, alterations in signal transduction, and possibly, a genetic link. To study this relation more closely, we investigated whether there are any differences in the clinical characteristics of BD patients with and without DM.

We compared the clinical data of 26 diabetic and 196 nondiabetic subjects from The Maritime Bipolar Registry. Subjects were aged 15 to 82 years, with psychiatric diagnoses of BD I (n = 151), BD II (n = 65), and BD not otherwise specified (n = 6). The registry included basic demographic data and details on the clinical course of bipolar illness, its treatment, and physical comorbidity. In a subsequent analysis using logistic regression, we examined the variables showing differences between groups, with diabetes as an outcome variable.

The prevalence of DM in our sample was 11.7% (n = 26). Diabetic patients were significantly older than nondiabetic patients (P < 0.001), had higher rates of rapid cycling (P = 0.02) and chronic course of BD (P = 0.006), scored lower on the Global Assessment of Functioning Scale (P = 0.01), were more often on disability for BD (P < 0.001), and had higher body mass index (P < 0.001) and increased frequency of hypertension (P = 0.003). Lifetime history of treatment with antipsychotics was not significantly associated with an elevated risk of diabetes (P = 0.16); however, the data showed a trend toward more frequent use of antipsychotic medication among diabetic subjects.

Our findings suggest that the diagnosis of DM in BD patients is relevant for their prognosis and outcome.

A growing body of data suggests that a significantly enhanced salivary cortisol response to waking may indicate an enduring tendency to abnormal cortisol regulation. Our objective was to apply the response test to a population already known to have long-term hypothalamo-pituitary-adrenocortical (HPA) axis dysregulation. We hypothesized that the free cortisol response to waking, believed to be genetically influenced, would be elevated in a significant percentage of cases, regardless of the afternoon Dexamethasone Suppression Test (DST) value.

Using the free cortisol response to waking and the short daytime profile, we tested 18 clinically stable, lithium-responsive subjects from our long-term naturalistic follow-up of monthly DSTs. These tests include salivary testing every 15 minutes during the first hour of waking, followed by samples taken at 3:00 PM and 8:00 PM.

While clinically stable on lithium prophylaxis, patients with bipolar disorder (BD) showed a significantly enhanced salivary cortisol response to waking, compared with control subjects (P < 0.03). Cortisol levels 30 minutes after waking significantly exceeded those in the large normative data provided in the literature (P < 0.001).

Our observations support the hypothesis that the free cortisol response to waking can reflect relatively enduring HPA dysregulation, even when lithium-responsive BD patients are clinically well and their DSTs are normal. Because the test is easy to administer, the free cortisol response to waking may hold promise as a marker in studies of high-risk families predisposed to, or at risk for, mood disorders.

To compare patients with and without mental disorders who seek services from a complementary therapy practitioner with regard to quality of life, reasons for seeking complementary therapies, complaints, and physical conditions.

We studied new patients who attended a complementary therapy clinic offering acupuncture treatment between July 1, 1993, and March 31, 1995. We collected data from a self-administered questionnaire and from a physician-conducted psychiatric assessment.

Of the 826 new patients at the clinic, 578 (70%) presented with a mental disorder. Patients with a mental disorder perceived their quality of life as poorer and reported greater levels of stress than did those without a mental disorder. However, the groups did not differ in their self-reported reasons for seeking complementary therapies, in their complaints, or in their physical conditions. Among patients with a mental disorder, the major reasons for choosing complementary therapies were personal preference, interest, or belief in complementary therapies (44.3%) and perceiving complementary therapies as a last resort (30.7%). Most patients with a mental disorder saw a complementary practitioner for musculoskeletal and connective-tissue disorders (44.1%), fatigue (26.6%), and headache (15.2%). The most frequent physical illnesses among patients with a mental disorder were diseases of the musculoskeletal system and connective tissue (42.6%).

Like their counterparts without a mental disorder, individuals with a mental disorder use complementary therapies because of personal beliefs. The wide use of complementary therapies among individuals with a mental disorder may be ascribed to a poor quality of life and high levels of distress.

The feasibility of clinical trials depends, among other factors, on the number of eligible patients, the recruitment process, and the readiness of patients to participate in research. Seeking patients' views about their experience in research projects may allow investigators to develop more effective recruitment and retention strategies.

A total of 100 patients consecutively admitted to a psychiatric university hospital were interviewed with respect to their willingness to participate in a study. For a different study scenario, patients were asked whether they would be ready to participate if such a study were organized in the service and to indicate their reasons for refusing or for participating.

The general readiness to participate in a study ranged between 70% and 96%. The prospect of remuneration did not notably augment the potential consent rate. The most common and spontaneous motivation for agreeing to take part in a study was to help science progress and to allow future patients to benefit from improved diagnosis and treatment (87%). The presence or lack of a financial incentive was rarely chosen as an argument to agree (23%) or to refuse (7%) to participate. Patients relied mainly on their treating physicians when contemplating possible participation in a study (family physician [65%] and hospital physician [54%]).

Clinicians and, in particular, treating doctors can play an important role in facilitating the recruitment process.

Scarce attention has been paid to establishing benchmarks for tertiary care for adults with severe mental disorders. Yet, the availability and efficient utilization of residential resources partly determines the capacity of a comprehensive system of care to avoid clogging ever-shrinking acute care bed facilities.

To describe the actual utilization of and projected needs for residential resources, one part of tertiary care, in the catchment area of a psychiatric hospital in east-end Montreal. To compare results obtained against actual utilization and projected needs evaluated in other Canadian provinces and in other countries, with a view to establishing national benchmarks.

Two surveys were undertaken to establish the number of places in these facilities that were utilized and needed for adults aged 18 to 65 years with severe mental disorders, without a primary diagnosis of mental retardation or organic brain syndrome, and originally from the catchment area. A first survey ascertained the number of places utilized and of those needed for residential care among all long-stay inpatients and all adults in supervised residential facilities. A second survey identified the need for such long-stay hospitalization, nursing homes, and supervised facilities as an alternative or as a complement to hospitalization among acute care inpatients.

The actual ratio of places in long-stay hospital units, nursing homes, and supervised residential facilities was 150:100 000 inhabitants. The ideal ratio, according to estimated needs, is 171:100 000. The figure breakdown is as follows: 20:100 000 for long-stay hospital units, 20:100 000 for nursing homes, 40:100 000 for group homes, 40:100 000 for private hostels or foster families, and 51:100 000 for supervised apartments. The needs of this urban, blue-collar population for supervised residential places hovered in the upper range of utilization and standards for European countries and within the proposed standards for Canadian provinces.

Needs for long-stay hospitalization or for supervised residential facilities cannot be treated as absolute. For example, evaluation conducted in this hospital-led system of psychiatric care may produce higher estimates of institutional care. Comparing actual utilization and projected needs in this urban catchment area with current utilization in other jurisdictions in Canada and Europe should contribute to establishing sound national benchmarks within ranges.

It is possible to establish benchmarks that guide the development of supervised residential settings to best meet the needs of the population of adults with severe and persistent mental disorders. The methods used here to assess needs should serve as guidelines for future research, because they were designed to contain the bias of over- or underprovision of care in the current utilization.

Patient attitudes toward mental illness are an important determinant of treatment compliance and treatment outcome. A patient's age, sex, style of thinking, lifestyle, and beliefs all may influence perceptions. This study aimed to determine patient attitudes.

Patients with a depressive disorder (n = 102) who were referred for psychiatric consultation and treatment to a community general hospital psychiatric outpatient clinic completed a 9-item self-report questionnaire to determine their perceptions of the biological, psychological, cognitive, and spiritual causes of their depressive disorder.

Women were more likely to endorse their depressive disorder as related to a biological abnormality. With respect to age, older individuals were less likely to identify cognitive factors and loss of spirituality as causal factors in their depression.

A relation exists between demographic variables, including sex and age, and beliefs about causes of depression and related disorders. These findings have implications for refining patient psychoeducation.