Evidence-based treatment strategies for treatment-resistant bipolar depression: A systematic review

Department of Mood Disorders ECT Department, University Psychiatric Center, Catholic University Leuven, Campus Kortenberg, Kortenberg, Belgium Department of Elderly Psychiatry, GGZ inGeest/VUmc, Amsterdam, The Netherlands Department of Psychiatry, General Hospital Sint-Jan Brugge-Oostende AV, Brugge, Belgium.
Bipolar Disorders (Impact Factor: 4.97). 11/2012; 15(1). DOI: 10.1111/bdi.12026
Source: PubMed


Treatment resistance in bipolar depression is a common clinical problem that constitutes a major challenge for the treating clinician as there is a paucity of treatment options. The objective of this paper was to review the evidence for treatment options in treatment-resistant bipolar depression, as found in randomized controlled trials and with special attention to the definition and assessment of treatment resistance.

A Medline search (from database inception to May 2012) was performed using the search terms treatment resistance or treatment refractory, and bipolar depression or bipolar disorder, supplemented with 43 separate searches using the various pharmacologic agents or technical interventions as search terms.

Only seven studies met our inclusion criteria. These studies examined the effects of ketamine (n = 1), (ar)modafinil (n = 2), pramipexole (n = 1), lamotrigine (n = 1), inositol (n = 1), risperidone (n = 1), and electroconvulsive therapy (ECT) (n = 2).

The available level I evidence for treatment strategies in resistant bipolar depression is extremely scarce, and although the response rates reported are reassuring, most of the strategies remain experimental. There is an urgent need for further study in homogeneous patient samples using a clear concept of treatment resistance.

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Available from: A. Dols, Sep 18, 2014
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    • "Mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD), are highly prevalent and debilitating conditions, associated with high suicidality rates, elevated treatment costs, and heavy social and economic burden [1]. The treatment of depressive episodes is associated with a 30–40% rate of nonresponse [2]. Few effective treatments are currently used and approved for resistant unipolar and bipolar depression. "
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    05/2015; 2015:1-9. DOI:10.1155/2015/521398
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    • "Modafinil and its R-enantiomer armodafinil (ar/mod) are approved treatments for excessive daytime sleepiness associated with narcolepsy, dayenight shift work sleep disorder, and obstructive sleep apnea (Nishino and Okuro, 2008). However, ar/ mod may have efficacy in other conditions such as bipolar depression (Sienaert et al., 2013), substance abuse (Mereu et al., 2013), and schizophrenia (Lindenmayer et al., 2013), as well. Modafinil increases the levels of dopamine, norepinephrine, and serotonin in the prefrontal cortex (de Saint Hilaire et al., 2001); dopamine levels are also elevated in the nucleus accumbens (Volkow et al., 2009). "
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    Journal of Psychiatric Research 09/2014; 60. DOI:10.1016/j.jpsychires.2014.09.013 · 3.96 Impact Factor
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    • "Mood disorders are among the commonest conditions presenting to psychiatrists for diagnosis and management.1) Major depressive disorder and bipolar disorders carry high rates of morbidity and mortality.2) Modern psychopharmacological agents often fall short of inducing remission and complex drug regimens are frequently needed to achieve symptom control.3) The past decade has witnessed an increase in the armamentarium of psychotropic medications for the treatment of mood disorders. "
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    Clinical Psychopharmacology and Neuroscience 08/2014; 12(2):157-9. DOI:10.9758/cpn.2014.12.2.157
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