Bipolar Depressive Subtypes, Other Clinical Factors, and Treatment Response
Although pharmacotherapy with lithium is an effective treatment for many patients with bipolar disorder, Maj and colleagues (1989)…

Conclusions
Treatment resistance is not a unitary phenomenon but in mood disorders reflects issues of diagnostic subtypes, comorbidity, and treatment adequacy, augmentation, and alternatives. In clinical practice, therefore, it is not…

Treatment-Resistant Unipolar Depression

Appendix: Multiphase Treatment Strategy for Bipolar Disorder

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Treatments to Control Cycling
As noted earlier, for about 90% of bipolar disorders, recurrence rather than persistence of acute episodes is the primary problem in psychopharmacological management. During the past two decades…

Treatment of Bipolar Depression
The algorithm presented for treatment-resistant bipolar depression (

Practical Management
Management of patients with treatment-resistant bipolar disorder is complicated by the need to be vigilant about the possibility of affective switch, as well as the current symptomatology targeted…

Other Treatment Options

Sleep Deprivation
Sleep deprivation to treat depression was first proposed by Schulte in 1969. Total sleep deprivation is defined as lack of sleep for an entire…

Treatment-Resistant Bipolar Disorder

Switching Strategies
When patients do not respond to treatment with one antidepressant, a common clinical strategy is to switch antidepressants. Although a change to an antidepressant of the same class…

Combined SSRIs and TCAs  The strategy of combining fluoxetine or other SSRIs with a TCA in the treatment of patients with refractory depression has been popular. An early…

SSRI-nefazodone combination  To date, only anecdotal reports have suggested the efficacy of combining SSRIs with nefazodone—typically at 100 or 200 mg bid. There is one report of this combination resulting…

Combined MAOIs and TCAs  Although in the 1960s combined antidepressant therapy with MAOIs and TCAs was more common, involving up to 5% of all antidepressant prescriptions (Tyrer and…

Combined Antidepressant Treatments
How should antidepressants be combined and for how long?  The term combination strategy in resistant depression typically refers to the addition to an antidepressant of…

Higher-Dose Antidepressants
What clinical trial evidence for the use of higher-dose antidepressants in treatment-refractory depression is available?  An alternative approach to switching is the use of relatively high doses…

Buspirone augmentation  One relatively user-friendly strategy is buspirone augmentation. Buspirone is typically a well-tolerated anti-anxiety drug, an azaspirodecanedione and a partial serotonin type 1 (5-HT₁) agonist. Three patients whose depression…

Dopaminergic and stimulant augmentation  Dopamine has received less attention than either serotonin or noradrenaline as a factor in the pathogenesis and treatment of depression, although preclinical and clinical…

Thyroid augmentation  The addition of thyroid hormone to an antidepressant in antidepressant nonresponders has been reported since the late 1960s. In one case series of women, thyroid hormone, when prescribed…

Treatment-Resistant Unipolar Depression: Antidepressant Treatment Options
If a depressed patient does not respond to an antidepressant after an optimized medication trial, the physician can choose one of four treatment strategies: augment the failed…

Treatment-Resistant Unipolar Depression: Depressive Subtypes and Treatment Response
Since the introduction of TCAs in the 1950s, clinicians and clinical researchers have attempted to define depressive subtypes to predict response to these…

Introduction

The introduction of monoamine oxidase inhibitors (MAOIs) and imipramine in the 1950s for…