Erasing the Personal Baseline: Graphing Responders to Psychiatric Drug Maintenance Therapy.

Since the 1950s, the practice of psychiatric drug maintenance therapy has been supported by graphics. Lacking physical markers to identify "responders" to long-term drugs, psychiatrists have used graphics to make the outcomes of their interventions visible. This article identifies changes in the graphical representation of drug responders in psychiatric journals between the mid-1950s and the mid-1990s. It argues that before 1970, psychiatrists assessed patients' responses in relation to their personal baselines or symptom trajectories. After 1970, clinical trials made it possible to see responders through a statistical lens, as a homogeneous population, decontextualized from its past and having a future consisting of two possible states: relapse or remission. Abstracted from their life's context, responders became the desired outcome of prescribing protocols that could be applied anywhere. Psychiatry's graphical language supported an authoritative view of mental health as something to be optimized and maintained with prescription drugs.

Recurrence rates in Ontario physicians monitored for major depression and bipolar disorder.

OBJECTIVE: Physicians with recurrent conditions that may affect job performance are sometimes referred for monitoring to help ensure compliance with treatment, ongoing remission of illness, and patient safety. Little is known about recurrence rates among doctors monitored for mood disorders. Our primary objective was to describe recurrence rates among Ontario physicians monitored for recurrent unipolar depression and bipolar disorder (BD). Our secondary objective was to explore predictors of recurrence. METHOD: We used a retrospective cohort design to describe the time to recurrence, defined as either stopping work owing to symptoms or any re-emergence of symptoms meeting a pre-established clinical threshold. Our exploratory analysis of recurrence predictors included age, sex, psychiatric diagnosis, psychiatric comorbidity, medical comorbidity, number of past episodes, past hospitalizations, and family history of psychiatric disorder. RESULTS: During a median observation of 24 months, 36% (18 of 50) of physicians stopped work owing to recurrence of symptoms, with the median time to stopping work being 11 months. As well, 52% (26 of 50) had a re-emergence of clinical symptoms, with the median time to any level of symptom re-emergence being 13 months. Physicians with psychiatric comorbidity stopped work sooner (hazard ratio [HR] 3.53; 95% CI 1.24 to 10.03, P = 0.01) and had more rapid symptom re-emergence (HR 2.96; 95% CI 1.34 to 6.52, P = 0.004) than those without comorbidity. The most common psychiatric comorbidity was a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, anxiety disorder. CONCLUSION: Recurrence rates are high among Ontario physicians referred for formal monitoring of recurrent unipolar depression and BD, and are markedly hastened by the presence of psychiatric comorbidity.

Selective serotonin reuptake inhibitors for unipolar depression: a systematic review of classic long-term randomized controlled trials.

BACKGROUND: Selective serotonin reuptake inhibitors are increasingly used in the long-term treatment of depression. Much of the supporting evidence about the effects of these drugs comes from discontinuation trials, a variant of randomized controlled trials whose design is problematic to interpret. We conducted a systematic review to examine the efficacy and acceptability of long-term therapy with selective serotonin reuptake inhibitors relative to placebo in the treatment of unipolar depression. METHODS: We identified placebo-controlled randomized trials with a treatment duration of at least 6 months by searching MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to update a recently published systematic review. Efficacy was defined in terms of response to treatment (50% improvement in depression score relative to baseline) and remission (score of 7 or below on the Hamilton rating scale for depression). Key secondary outcomes included quality of life, return to work, need for additional treatment and self-harm. Overall acceptability was defined in terms of dropouts for any reason over a course of treatment. RESULTS: Of the 2693 records identified initially, we included 6 randomized controlled trials that met our eligibility criteria. These studies had a moderate risk of bias, had assigned a total of 1299 participants with depression to either treatment or placebo and had followed both groups for 6-8 months. We observed statistically significant improvements in response to treatment (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.12-2.48), but not in remission (OR 1.46, 95% CI 0.92-2.32) or acceptability (OR 0.87, 95% CI 0.67-1.14). The effects appeared greater among patients without comorbidities. INTERPRETATION: There is a lack of classic randomized controlled trials of serotonin reuptake inhibitors lasting more than 1 year for the treatment of depression. The results of our systematic review support current recommendations for 6-8 months of antidepressant treatment following initial recovery but provide no guidance for longer treatment.

Salivary cortisol secretion in remitted bipolar patients and offspring of bipolar parents.

OBJECTIVES: It is generally believed that cortisol secretion normalizes during clinical remission in mood disorders. However, this assumption has been challenged by preliminary reports of enhanced cortisol secretion in remitted bipolar patients and in the offspring of bipolar parents. The purpose of this study is to replicate findings of increased cortisol secretion during clinical remission in bipolar patients and in the offspring of bipolar parents, rigorously controlling for known confounders. METHODS: We conducted intensive cortisol sampling (six samples per day for three test days, on three consecutive weekends) on 15 bipolar type I and type II patients and 28 unrelated offspring of bipolar parents. Offspring had a history of unipolar depression. Participation was restricted to cases in complete sustained remission. Controls were matched as closely as possible for age, sex, and education. Mood and sleep measures were recorded on each sampling day. RESULTS: In total, 743 samples were collected from the patient group and 576 from controls. Correcting for repeat measures, there was no statistically significant difference in cortisol secretion at any sampling time between remitted bipolar patients, remitted offspring of bipolar parents, and normal controls. The cortisol waking response did not differ between patients and controls. Covariates, including sex, age, Beck depression score and hours of sleep, were not statistically significant. CONCLUSIONS: Our observations are consistent with the view that complete sustained clinical remission is associated with normal salivary cortisol levels throughout the day. A personal or family history of bipolar disorder per se does not appear to confer added risk for increased salivary cortisol secretion during sustained clinical remission.

MMPI as a measure of subthreshold and residual psychopathology among the offspring of lithium responsive and non-responsive bipolar parents.

OBJECTIVES: In bipolar adults, the Minnesota Multiphasic Personality Inventory (MMPI) can detect residual symptoms and confirm completeness of remission, thus helping to predict response to lithium prophylaxis. In the high-risk and early onset bipolar populations, the association of the MMPI with clinical course and treatment response has not yet been studied. The present study compares MMPI profiles completed by the well or remitted offspring of two groups of bipolar parents divided on the basis of parental response to long-term lithium. METHODS: As part of an ongoing prospective longitudinal high-risk study, offspring of bipolar parents determined to either respond or not respond to long-term lithium monotherapy completed the MMPI. At the time of MMPI completion, offspring were determined to be either well (unaffected) or clinically remitted (affected but euthymic) based on repeated prospective KSADS-PL format interviews conducted by a research psychiatrist and reviewed on a blind consensus basis. RESULTS: While there was no difference in the MMPI scores between subgroups of unaffected offspring, there was a significant difference in profiles between remitted offspring. Specifically, affected offspring of lithium non-responders showed significantly higher average scores on scales 6, 8 and 0 compared with affected offspring of lithium responders. These findings are consistent with the differences in MMPI profiles taken at optimum between the respective parent subgroups. CONCLUSIONS: The findings confirm the clinical observation that the affected offspring of lithium responders suffer from episodic fully remitting mood disorders, while the affected offspring of lithium non-responders suffer from mood disorders with incomplete remission. Further, the nature of the residual symptoms as indicated by the abnormal MMPIs support the view of heterogeneity of the bipolar diagnosis. The relevance to treatment response is discussed.

The cortisol awakening response in bipolar illness: a pilot study.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.

Descartes' Passions of the soul--seeds of psychiatry?

Rene Descartes (1596-1650), often called the 'father of modern philosophy', aimed at rooting all knowledge in certainty so that our understanding of the world could progress without error. To achieve this, he needed at least one sure thing on which to build. Starting with the most basic knowledge, the fact of his own existence--cogito ergo sum (I think therefore I am), he systematically proceeded to explain the world. Such systematic understanding would be accessible to anyone who applied the Cartesian method, and in turn would lead to a good life. Descartes' Passions of the Soul was written according to his method of certainty and fits in with a meticulously refined worldview. It is one of the first systematic treatises to explain a wide array of emotions, both normal and abnormal. Based on the Cartesian dualistic model of mind and body, the work helps ground a long medical tradition of separating 'rational' consciousness from emotions. For Descartes, emotions arose from two sources, the intellect and the body (Passions of the Soul and Passions of the Body). The more subtle 'Passions of the Soul' were viewed as superior to coarser and often-troublesome emotions taking root in the body. It is interesting to note the absence of clarity, however, in Descartes' division of intellectual emotions from bodily emotions, perhaps revealing an enduring weakness in the dualistic model itself. The work grapples with the multi-causal nature of psychopathology and brings out complex interactions between temperament and life experience. While modern neuroscience makes ever-tighter associations between physiology and experience, many of the basic scientific challenges we face today are outlined in this 350-year-old book.