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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article reviews recent developments in the pharmacotherapy of mood disorders. Pharmacotherapy is the best studied and most widely validated approach for acute phase treatment and prevention of relapse-recurrence for patients with major depression, dysthymia, and bipolar affective disorder. Antidepressants are also the mainstay of inpatient treatment and, when considered together with electroconvulsive therapy, represent the first line of treatment for the most severe and incapacitating forms of depression. Similarly, pharmacotherapy with mood stabilizers is the first line of treatment for bipolar depression and mania. Despite such efficacy, problems associated with pharmacotherapy include acceptability, tolerability, adherence, incomplete remission, and high rates of recurrence after drug discontinuation. Moreover, a small subset of patients do not respond to multiple medication trials.
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PMID:Recent developments in the pharmacotherapy of mood disorders. 880 54

Patients with treatment-resistant bipolar depression require careful management, which takes into account the life-threatening potential of their depression and the risk of iatrogenic mania. Because there are few data specific to treatment of bipolar depression, much of the approach to bipolar depression is derived from experience with unipolar depression. There are, however, important differences between these two illnesses. Compared with patients with unipolar illness, patients with bipolar depression more likely experience antidepressant benefit from mood-stabilizing medication and, therefore, avoid the risks of antidepressant medication. Treatment of comorbid anxiety and substance abuse improves response. The risk of treating bipolar patients can be reduced but not avoided. Improved outcome may be achieved by careful assessment, prospective mood charting, and attempts to taper antidepressant medications after an appropriate continuation phase.
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PMID:Treatment-resistant bipolar depression. 882 87

When faced with a patient having treatment-resistant depression, it is essential to maintain a systematic approach to diagnosis and treatment: 1. Consider the presence of comorbid medical or psychiatric illness that may contribute to or cause the refractory state 2. Determine the affective subtype of depression (e.g., unipolar vs. phenotypic variant of bipolar depression) 3. Ensure the presence of adequate antidepressant dosage, plasma concentrations (where applicable), and duration of treatment 4. Apply systematic treatment algorithms, which means (1) initiate the most efficacious "first-line" therapy for a specific depressive subtype (even if that is an MAOI) and (2) initiate augmentation strategies in a systematic fashion. Augmentation strategies should be initiated only after first reviewing prior therapy, considering available treatment alternatives, and examining the relative risk:benefit ratio for each treatment option in the current clinical context. Following these guidelines should prevent the development of "therapeutic nihilism" in both the patient and physician, as well as enhance the ultimate treatment outcome for patients with treatment-resistant depression.
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PMID:Treatment algorithms in treatment-resistant depression. 882 95

Acute bipolar depression (ABD) and breakthrough depression occurring during maintenance therapy of bipolar disorder are associated with significant morbidity and an increased risk of suicide. Lithium is an effective mood stabilizer for ABD, but its onset of antidepressant action is slow and additional antidepressant therapy is often prescribed. The extent to which other mood stabilizers (e.g., carbamazepine and valproate) have antidepressant activity is unclear. Preliminary initial research suggests three potential advantages that selective serotonin reuptake inhibitors have over tricyclic antidepressant for ABD: possibly greater efficacy, fewer adverse effects, and a lower frequency of antidepressant-induced mania. Bupropion may also have significant advantages. However, further research is needed to confirm these findings. Monoamine oxidase inhibitors are the antidepressant of choice for atypical bipolar depression. Electroconvulsive therapy (ECT) has the highest response rate of all treatments for ABD. Further research is needed to explore combination treatments with mood stabilizers and antidepressants for the effective treatment of ABD.
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PMID:Management of the depressive component of bipolar disorder. 916 51

We sought to determine whether depressive and mixed/cycling episodes were as responsive to standardized pharmacotherapeutic interventions as were manic episodes in bipolar 1 patients. As part of the Maintenance Therapies in Bipolar Disorder (MH29618, E. Frank, PI) study, forty-two acutely ill bipolar 1 patients who had been randomly assigned to one of two preliminary phase non-pharmacologic treatment strategies (interpersonal and social rhythm therapy [IPSRT] or a standard medication clinic approach) were treated according to a standardized pharmacotherapeutic protocol. Symptom severity was measured weekly with the Hamilton Depression Rating Scale and the Bech-Rafaelsen Mania Scale in order to assess symptomatic remission. Survival analysis with the proportional hazards model was performed on time to remission. Manic patients were significantly more likely to achieve clinical remission than the depressed patients (100 vs. 59%) and did so significantly more rapidly. The difference in proportion remitting and time to remission between the depressed and mixed/cycling groups was not statistically significant. No significant effect for non-pharmacologic treatment assignment was found. These results point to the need to develop more effective treatments for bipolar depression. They also suggest that psychotherapy has a limited impact in the acute phase treatment of bipolar episodes.
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PMID:Bipolar depression: an underestimated treatment challenge. 926 37

Thus, there appears to be a large variety of approaches to refractory bipolar depression. In contrast to several decades ago, wherein augmentation of lithium with antidepressants and neuroleptics was essentially the only treatment mode available, a panoply of treatment options now exist. However, their relative efficacy in different illness subtypes and stages remains to be better delineated, as do their optimal sequencing and use in combination in individual patients. It is the opinion of these authors and many of our colleagues in the field that initial use of several mood stabilizer drugs in combination may have a preferable long-term outcome in some rapid cycling patients, compared with the immediate use of a unimodal antidepressant with an inadequate single mood stabilizer, although this remains to be systematically studied. The use of thyroid augmentation strategies would appear to have merit in relationship to not only the potential treatment of lithium-related hypothyroidism, but also in augmenting antimanic and antidepressant effects. As one moves toward some of the complex combination treatment strategies discussed in this chapter, one has to be particularly careful about drug interactions and their potential for toxicity as well as therapeutic effects. Perhaps a prevailing guideline would be to use these agents more carefully in combination therapy than in monotherapy, with slow upward titration of dose to individual patients' side effects thresholds, even in preference to targeting of conventional blood level windows. In this way, side effects can be avoided during the assessment of complex combination regimens. In addition, one should be aware of potential pharmacokinetic interactions. For example, with the addition of valproate to carbamazenine, one should reduce the dose of carbamazepine, as valproate will not only increase the free fraction of carbamazepine based on displacement of protein binding, but will lead to increased accumulation of carbamazepine-10,11-epoxide. This epoxide is not measured in conventional assays but could contribute to the side effects profile (Ketter and Post, 1994). Similarly, valproate will markedly increase blood levels of lamotrigine; the starting dose of this agent should be substantially lower than conventional dosage when these two drugs are used in combination. We suggest the utility of detailed mapping with a formal system-such as the Life Chart Methodology (LCM) (Leverich and Post, 1996)-of mood fluctuation vs. medications in order to optimize and rationalize complex combination therapy. In this way, not only can the nuances of partial response be better defined, but also basic decisions about the therapeutic index and relative likelihood of response can be more readily assessed. We have discussed the other merits of the life chart method as an important clinical treatment tool as well as a research tool in other venues, but reemphasize its potential great importance in the treatment of refractory cyclic bipolar patients, in whom an initial period of remission of depression may, in many instances, be as likely attributable to the natural course of illness as the current intervention being offered. As such, it behooves the clinician to have a systematic database for the more subtle issues of dose titration and sequential addition of medications in complex combination regimens. In the face of inefficiency to one combination strategy, how one moves to the next strategy remains a highly individualized, clinically-based algorithm. We suggest the potential utility of moving towards a new set of mood stabilizers and then repeating some of the unimodal antidepressant additions and augmentation trials in an attempt to overcome refractory depression. Refractory depression in bipolar patients should be viewed as a medical emergency in light of the high potential for suicide in the illness in general (Chen and Dilsaver, 1996) and in patients who have either sustained or episodic refracto
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PMID:Alternative approaches to refractory depression in bipolar illness. 933 10

Altered locomotor activity is a cardinal sign of several psychiatric disorders. With advances in technology, activity can now be measured precisely. Contemporary studies quantifying activity in psychiatric patients are reviewed. Studies were located by a Medline search (1965 to present; English language only) cross-referencing motor activity and major psychiatric disorders. The review focused on mood disorders and attention-deficit hyperactivity disorder (ADHD). Activity levels are elevated in mania, agitated depression, and ADHD and attenuated in bipolar depression and seasonal depression. The percentage of low-level daytime activity is directly related to severity of depression, and change in this parameter accurately mirrors recovery. Demanding cognitive tasks elicit fidgeting in children with ADHD, and precise measures of activity and attention may provide a sensitive and specific marker for this disorder. Circadian rhythm analysis enhances the sophistication of activity measures. Affective disorders in children and adolescents are characterized by an attenuated circadian rhythm and an enhanced 12-hour harmonic rhythm (diurnal variation). Circadian analysis may help to distinguish between the activity patterns of mania (dysregulated) and ADHD (intact or enhanced). Persistence of hyperactivity or circadian dysregulation in bipolar patients treated with lithium appears to predict rapid relapse once medication is discontinued. Activity monitoring is a valuable research tool, with the potential to aid clinicians in diagnosis and in prediction of treatment response.
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PMID:Actigraphy and motion analysis: new tools for psychiatry. 938 25

Gender differences in bipolar illness have been relatively neglected, but the course of the illness does appear to differ between men and women. Compared with bipolar men, bipolar women are clearly more likely to develop the rapid cycling form of the illness and may also suffer from more episodes of depression. Therefore, the literature concerning the treatment of rapid cycling bipolar disorder and of bipolar depression is reviewed. In addition, effects of bipolar illness on the female reproductive cycle are discussed. Since bipolar women are at high risk to develop postpartum episodes, the use of mood stabilizers in pregnancy is discussed.
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PMID:Issues in the treatment of women with bipolar illness. 942 71

1. Structural neuropathologic abnormalities have been associated with severe psychiatric illnesses, including bipolar disorder, major depressive disorder, and schizophrenia. In the latter, ventricular enlargement has been variably associated with symptom severity and poor treatment response. In patients with severe depressive disorders, the relationship between cortical and subcortical pathology and ventricle enlargement, symptom severity, and response to treatment is far from clear. 2. The present study investigated the relationship between structural CNS pathology, symptom severity and treatment response in patients undergoing ECT. It was hypothesized that patients with greater neuroanatomic abnormalities would demonstrate greater initial symptom severity and poorer response to ECT. 3. The subjects were 57 patients with unipolar or bipolar depression admitted for ECT treatment. Symptom severity was quantified using the Hamilton Depression Rating Scale (HRSD) at baseline and post-ECT. 4. Lateral and third ventricle-brain ratio (LVBR, 3VBR) were determined from CT scans and cortical atrophy was rated by a faculty neuroradiologist. 5. Contrary to our first hypothesis, structural pathology was not associated with baseline symptom severity. In terms of treatment response, the number of treatments required to achieve benefit was correlated with larger 3VBR; CT variables were not related to total post-treatment or change in HRSD score. Third ventricle enlargement may be an index of generalized pathology or regional brainstem abnormalities that influence ECT response rate by limiting individual seizure efficacy or neurochemical responsiveness, thereby necessitating a greater number of ECT treatments, without significant impact on overall response.
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PMID:Does neuroanatomy predict ECT response? 946 96

Most of the randomized controlled trials (RCTs) on the acute treatment of children and adolescents with major depressive disorder (MDD) have shown about 50 percent response to both tricyclic antidepressants (TCAs) and placebo. In contrast, a recent RCT found fluoxetine superior to placebo for the treatment of depressed youth. Cognitive-behavioral psychotherapy has also been found efficacious for the treatment of youth with depression. Therefore, the use of medications in particular TCAs, as the first line of treatment for youth with mild to moderate MDD has been questioned. However, some subgroups of patients, especially those who are unable or unwilling to undergo psychotherapy and those with psychosis, bipolar depression, severe depressions, or recurrent episodes, may benefit from initial treatment with antidepressants. Further research on the continuation and maintenance treatment phases of depression as well as treatment for dysthymia, treatment-resistant depression, and other subtypes of depressions is warranted.
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PMID:Should we use antidepressant medications for children and adolescents with depressive disorders? 956 96


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