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P S Y C H O P H A R M A C O L O G Y B U L L E T I N: Vol. 41 · No. 3 • 91 Placebo Response in Depression: A Perspective for Clinical Practice By Arif Khan, Shirin Khan Khan A, MD, Northwest Clinical Research Center, Bellevue, Washington, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina. Khan S, BS, Northwest Clinical Research Center, Bellevue, Washington. To whom correspondence should be addressed: Arif Khan, MD, Northwest Clinical Research Center, 1900—116th Ave NE, Bellevue, WA 98004, Phone: 425-453-0404; Fax: 425-453-1033; Email: [email protected] ABSTRACT ~ Practicing clinicians appre c i a te that depression is not an easy disorder to treat and manage. D e s p i te the plethora of new treatments—both pharmacological and non pharmacological—that has flooded the market in the past years, we are still nowhere close to obtaining full symptom rel i ef for all patients and erad i cating the morbidity and mortality associated with depression. In this context, recent methodological re s e a rch , concentrating on the ef f e c t iveness of a n t i- depressants has raised doubts about their therapeutic index. Because of obtuseness of the methodology and biased interpretations, we are submitting this per s p e c t ive to clinicians so that they can appreciate some of the deficits of the recent research publications. For the practicing clinician, the best available data suggest that clinically depressed patients war- rant treatment and the most robust available body of d a ta (published and unpublished) would favor the use of a n t i d e p re s s a n t s . Ps yc h o ph a r m a c o l o g y Bul l e t i n . 2008;41(3):91–98. INTRODUCTION Depression is a chronic and fluctuating disorder. Symptoms and signs of depression, along with level of psychological distress and level of functioning, for most patients wax and wane over time. There is not a single profile of symptoms and signs, as evidenced by changing definition of depression by the American Psychiatric Association (Diagnostic and Statistical Manual of Mental Disorders versions II, III, IV) over the past fifty years. There is no unifying concept on the etiology and pathophysiology of depression, or the acute treatment and ch ronic management of depressed patients. Experienced clinicians know that treating depression, albeit a simple disorder is not just reach- ing for the prescription pad and automatically knowing the best drug/treatment for each patient.Although there is a plethora of phys i cal (Electric Conv u l s i ve T h e rapy (ECT) and Vagus Nerve Stimulation (VNS)), pharmacological (32 anti- depressants in the United States) and psychological treatments (cognitive behav- i o ral therapy, interpersonal therapy) for depression, managing each individual patient requires patience, humility, and wisdom (Tri vedi et al. 1 ). Key Words: depression, antidepressants, clinical trials, clinical practice, placebo, placebo response GENERAL PSYCHIAT RY PB-41-3-2008-Khan.qxd 10/13/08 12:41 PM Page 91
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Transcript of placebo article
PS Y C H O P H A R M A C O L O G Y BU L L E T I N: Vol. 41 · No. 3 • 91
Placebo Response in Depression:A Perspective for Clinical Practice
By Arif Khan, Shirin Khan
Khan A, MD, Northwest Clinical Research Center, Bellevue, Washington, Department ofPsychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.Khan S, BS, Northwest Clinical Research Center, Bellevue, Washington.
To whom correspondence should be addressed: Arif Khan, MD, Northwest Clinical ResearchCenter, 1900—116th Ave NE, Bellevue, WA 98004, Phone: 425-453-0404; Fax: 425-453-1033;Email: [email protected]
A B STRA CT ~ Practicing clinicians ap p re c i a te that depression is not an easy disord er totreat and manage. D e s p i te the plethora of n ew treatments—both pharm ac o l o g i cal andnon pharmacological—that has flooded the market in the past years, we are still nowhereclose to obtaining full symptom rel i ef for all patients and erad i cating the morbidity andmortality associated with depression.In this contex t , recent methodological re s e a rch , c o n c e n trating on the ef f e c t iveness of a n t i-d e p ressants has raised doubts about their therapeutic index . B e cause of o b tuseness of t h em e t h o d o l o gy and biased interp re ta t i o n s , we are submitting this per s p e c t ive to cliniciansso that they can appreciate some of the deficits of the recent research publications. For thepracticing clinician, the best available data suggest that clinically depressed patients war-rant treatment and the most robust ava i l a ble body of d a ta (published and unpubl i s h e d )would favor the use of a n t i d e p re s s a n t s . Ps ych o ph a rm a c o l o gy Bull e t i n .2008;41(3):91–98.
INTRODUCTION
Depression is a chronic and fluctuating disorder. Symptoms and signs ofdepression, along with level of psychological distress and level of functioning, formost patients wax and wane over time. There is not a single profile of symptomsand signs, as evidenced by changing definition of depression by the AmericanPsychiatric Association (Diagnostic and Statistical Manual of Mental Disordersversions II, III, IV) over the past fifty years.
T h e re is no unifying concept on the etiology and pathophys i o l o gy of depre s s i on ,or the acute treatment and ch ronic management of depressed patients. E x p e ri e n c e dclinicians know that treating depre s s i on , albeit a simple disorder is not just re a ch-ing for the pre s c ri p t i on pad and autom a t i ca lly knowing the best dru g / t re a t m e n tfor each patient. Although there is a plethora of phys i cal (Electric Conv u l s i veT h e rapy (ECT) and Vagus Ne rve St i mu l a t i on (V N S ) ) , ph a rm a c o l o g i ca l (32 anti-d e p ressants in the United States) and psych o l o g i cal treatments (cognitive behav-i o ral thera p y, i n t e rp e r s onal therapy) for depre s s i on , managing each individualpatient re q u i res patience, h u m i l i ty, and wisdom (Tri vedi et al.1) .
Key Words: depression, antidepressants, clinical trials, clinical practice, placebo, placebo response
GENERAL PSYCHIAT RY
PB-41-3-2008-Khan.qxd 10/13/08 12:41 PM Page 91
Given this background, with the introduction of over a dozen newantidepressants in the past two decades, there has been a sense of hopeand optimism in managing depressed patients. However, research in thepast decade has shown that these newer agents are not necessarily bet-ter than earlier ones, but they however are easier to use, have fewer sideeffects, and are generally safer if taken in overdose.
In this con t e x t , two recent publica t i ons (Tu rner et al.2 and Kirsch et al.3)with high media cove rage have raised further con c e rns about the use-fulness and the therapeutic index of our current antidepre s s a n t s .M u ch of the data that they presented are well known to research psy-chiatrists, but may not have filtered to practicing clinicians.
In this perspective, we aim to provide a background of developmentalhurdles for depression treatments, the nature of placebo response,review recent publications in the context of clinical trial research, andlastly highlight the role of placebo response for non-specific treatmentfactors in clinical practice.
PS Y C H O P H A R M A C O L O G Y BU L L E T I N: Vol. 41 · No. 3
PLACEBO RESPONSE IN DEPRESSION: A PERSPECTIVE FOR CLINICAL PRACTICE
92Khan A, Khan S
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