Introduction Underlying Causes and Implications

Introduction Underlying Causes and Implications

treatment-resistant psychiatric disordersThe articles in this Special Report reflect the growing recognition of the importance of the problem of treatment-resistant psychiatric disorders. Mintz and Belnap1 recently reported that Medline citations on treatment-resistant psychiatric disorders increased 800% over the previous 20 years, while the overall number of citations increased 25%. Despite significant advances in neurobiology and psychopharmacology, we have become increasingly aware of the limitations of treatment for most psychiatric illnesses and that a significant number of psychiatric patients will not experience full recovery.2

This Special Report includes articles that summarize what is known about treatment resistance in a number of disorders. There is also an article that argues for the value of psychodynamic psychopharmacology, a notion advanced by Mintz and Belnap,1 in prescribing for patients with treatment-resistant disorders.

Two significant issues exist in relation to treatment resistance. Both represent an unfortunate trend toward tunnel vision about psychiatric disorders and about treatments that hinder our ability to help our patients.

First, we lack a uniform definition of treatment resistance that is applicable across a range of disorders. The current disorder-specific approach to defining and responding to treatment resistance is inconsistent with the growing evidence that suggests treatment resistance is often associated with significant comorbidity with other Axis I and II disorders. For example, in major depressive disorder (MDD), the Collaborative Longitudinal Personality Disorders Study has shown that personality disorders adversely affect outcome and are associated with persistent functional impairment, extensive treatment use, and significant suicide risk.3,4 In a meta-analysis of studies of a group of patients with complex, comorbid conditions, Leichsenring and Rabung5 found that patients who received long-term psychodynamic psychotherapy had better outcomes than 96% of comparable patients who received shorter-term therapies. It is puzzling that in spite of the current disorder-specific approach to treatment resistance, the series of American Psychiatric Association practice guidelines for psychiatric disorders do not systematically address the problem of treatment resistance.

A second relevant issue is a tendency to drift relentlessly toward viewing treatment resistance through a reductionistic biological lens. Too often, papers on treatment resistance focus on little more than the failure of biological treatments for the acute phase of disorders that are generally chronic and that are associated with significant psychosocial dysfunction during both acute and maintenance phases. For example, only about half of patients with bipolar disorder respond fully to acute phase treatment, and half experience a relapse within 2 years.6 There is also evidence that even patients who do not relapse manifest persistent executive functioning deficits that interfere with full recovery.

Rational medication algorithms based on the best available evidence and an emphasis on ensuring treatment adherence are essential. Beyond that, however, clinicians know that treatment resistance includes more than failure to respond to prescribed medications. It is often associated with multiple failed treatments, a course that involves chronic crisis management, maladaptive functioning between appointments, suicidal behavior, multiple short-term hospitalizations, markedly impaired interpersonal and vocational functioning, and markedly increased treatment costs.7

If our goal is to move beyond a profession limited to prescribing the same 50 or so medications for all psychiatric disorders, we need to attend to more than medications in our thinking about what constitutes treatment resistance and how to respond to it. For example, Nemeroff and colleagues8 found that the group of treatment-resistant patients with chronic MDD and a history of trauma responded better to psychotherapy than to medications.

We have learned much to help us better serve our patients, but there is much we still need to learn to best serve our patients with treatment-resistant disorders.



1. Mintz D, Belnap B. A view from Riggs: treatment resistance and patient authority, III: what is psychodynamic psychopharmacology? An approach to pharmacologic treatment resistance. J Am Acad Psychoanal Dyn Psychiatry. 2006;34:581-601.
2. Plakun EM. A view from Riggs: treatment resistance and patient authority, I: a psychodynamic perspective on treatment resistance. J Am Acad Psychoanal Dyn Psychiatry. 2006;34:349-366.
3. Skodol AE, Gunderson JG, Shea MT, et al. The Collaborative Longitudinal Personality Disorders Study (CLPS): overview and implications. J Pers Disord. 2005;19:487-504.
4. Bender DS, Skodol AE, Pagano ME, et al. Prospective assessment of treatment use by patients with personality disorders. Psychiatr Serv. 2006;57:254-257.
5.Leichsenring F, Rabung S. Effectiveness of long-term psychodynamic psychotherapy: a meta-analysis. JAMA. 2008;300:1551-1565.
6. Perlis RH, Ostacher MJ, Patel JK, et al. Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry. 2006;163:217-224.
7. Crown WH, Finkelstein S, Berndt ER, et al. The impact of treatment-resistant depression on health care utilization and costs. J Clin Psychiatry. 2002;63:963-971.
8. Nemeroff CB, Heim CM, Thase ME, et al. Differential response to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma [published correction appears in Proc Natl Acad Sci U S A. 2005;102: 16530]. Proc Natl Acad Sci U S A. 2003;100:14293-14296.

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