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The "Chemical Imbalance" Explanation for Depression: Origins, Lay Endorsement, and Clinical Implications

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Abstract

When a client asks whether her or his depression is caused by a chemical imbalance, how do you respond? Depression is regularly depicted in popular media as resulting from a "chemical imbalance" and this depiction raises a number of interesting questions for practicing clinicians. How accurate is the chemical imbalance explanation for depression? How widely do laypersons agree with the explanation, and how do they interpret the explanation? We discuss the origins, accuracy, and transmittal (e.g., via direct-to-consumer advertising) of the chemical imbalance explanation for depression. We next present results from a group case study examining lay endorsement and interpretation of the explanation. Finally, we discuss clinical implications and present a short script for educating clients concerning "chemical imbalances" in depression.
The “Chemical Imbalance” Explanation for Depression:
Origins, Lay Endorsement, and Clinical Implications
Christopher M. France
Cleveland State University
Paul H. Lysaker
Roudebush Veterans Affairs Medical Center, Indianapolis, and
Indiana University School of Medicine
Ryan P. Robinson
University of Akron
When a client asks whether her or his depression is caused by a chemical imbalance, how do you
respond? Depression is regularly depicted in popular media as resulting from a “chemical imbalance” and
this depiction raises a number of interesting questions for practicing clinicians. How accurate is the
chemical imbalance explanation for depression? How widely do laypersons agree with the explanation,
and how do they interpret the explanation? We discuss the origins, accuracy, and transmittal (e.g., via
direct-to-consumer advertising) of the chemical imbalance explanation for depression. We next present
results from a group case study examining lay endorsement and interpretation of the explanation. Finally,
we discuss clinical implications and present a short script for educating clients concerning “chemical
imbalances” in depression.
Keywords: chemical imbalance, depression, laypersons, direct-to-consumer advertising, monoamines
It is common in the United States for depression to be described
as resulting from a “chemical imbalance” (e.g., Valenstein, 1998).
As the potentially dominant cultural story of depression etiology,
the chemical imbalance explanation may exert a significant effect
on treatment-seeking behaviors as well as the structures that are
created and maintained for such treatment (e.g., Smith, 1999; also
see Rothman, 1971). As such, it appears important for mental
health professionals and other stakeholders (e.g., policymakers) to
understand lay beliefs concerning chemical imbalance explana-
tions for depression.
We do not dispute the possibility that neurotransmitters and
other brain chemicals play a significant role in the etiology of
depression. However, we are also concerned that the chemical
imbalance explanation may not reflect the full range of causes of
depression, may be given greater credence by both consumers and
practitioners than is supported by sound research, and/or may be
understood in an overly simplistic manner. Any unitary under-
standing of human suffering asserted in isolation of its nuances
may mislead those in need of treatment and confound self-
understanding, resulting in treatment-seeking strategies and out-
comes that are less than optimal for at least some clients.
The Development of Chemical Imbalance Explanations
for Depression
Modern chemical imbalance hypotheses of depression origi-
nated in the mid-20th century, spurred by important discoveries
such as the efficacy of chlorpromazine for psychosis; findings that
monoamines exist within the central nervous system (CNS) and act
as neurotransmitters; and an early understanding of monoamine
synthesis, storage, release, and deactivation. Such discoveries also
quickened the emergence of psychopharmacology as a discipline
and helped lead to the eventual widespread practice of using
prescription drugs to treat mental disorders also (e.g., Healy,
2001).
Iproniazid and Imipramine
The 1950s saw the appearance of the first antidepressant drugs
of the modern era, two being iproniazid and imipramine (Healy,
1997). Iproniazid’s initial importance was as an effective tubercu-
losis treatment, but it was also noted that some tubercular patients
CHRISTOPHER M. FRANCE received his PsyD in clinical psychology from
Wright State University. He is an assistant psychology professor at Cleve-
land State University and a licensed psychologist. His research interests
include cultural and personal conceptions of mental disorders and their
treatment.
PAUL H. LYSAKER received his PhD in clinical psychology from Kent State
University. He is a staff clinical psychologist at the Roudebush Veterans
Affairs Medical Center, Day Hospital 116H, and an assistant clinical
professor of psychology at the Indiana University School of Medicine,
Department of Psychiatry. His major areas of interest include vocational
rehabilitation, personal narratives, and recovery from severe mental illness.
RYAN P. ROBINSON received his MA in industrial organizational psychol-
ogy from the University of Akron, where he is also a doctoral candidate in
industrial organizational psychology. He is also a part-time lecturer at
Cleveland State University. His areas of interest include employee training
and development, affective reactions in the workplace, and research meth-
ods and statistics.
WE THANK Heather Dukes for assisting with background research and data
organization.
CORRESPONDENCE CONCERNING THIS ARTICLE should be addressed to Chris-
topher M. France, Department of Psychology, Cleveland State University,
Chester Building 159, 2121 Euclid Avenue, Cleveland, OH 44115. E-mail:
c.m.france@csuohio.edu
Professional Psychology: Research and Practice Copyright 2007 by the American Psychological Association
2007, Vol. 38, No. 4, 411–420 0735-7028/07/$12.00 DOI: 10.1037/0735-7028.38.4.411
411
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The pharmacokinetic profile of tianeptine is not altered in patients with alcoholic cirrhosis and depression. Therapeutic Efficacy The clinical antidepressant efficacy of tianeptine 25 to 50 mg/day has been proven against placebo in patients aged 18 to 60 years with major depression (single episode or recurrent) or bipolar disorder (depressed) in 2 double-blind trials. Initial improvements were seen after 7 days, and improvement continued throughout the 6 weeks of study. Improvements from baseline on the Montgomery-Åsberg Depression Rating Scale (MÅDRS) were 44 and 54% with tianeptine and 28 and 38% in placebo recipients (p < 0.05 and p < 0.01, respectively). Tianeptine 25 to 37.5 mg/day for 1.5 to 3 months had equivalent antidepressant efficacy to fluoxetine 20 mg/day in patients with major depression (single episode or recurrent), bipolar disorder (depressed) or dysthymic disorder in several studies. However, although equivalence was noted in several parameters in elderly patients receiving tianeptine or fluoxetine in one study, reductions from baseline in the MÅDRS scores were statistically significantly greater in those receiving fluoxetine (62 vs 51% in fluoxetine and tianeptine recipients, respectively, compared with 50 vs 51%, respectively, in a study in patients aged 18 to 65 years which used this assessment tool). The antidepressant efficacy of tianeptine 37.5 mg/day (reduction in MÅDRS score of 56%) was equivalent to that of sertraline 50 mg/day (reduction of 54%) after 1.5 months in patients with major depression or bipolar disorder. A study published only in abstract form indicates that tianeptine 37.5 mg/day has similar efficacy to paroxetine 20 mg/day for 3 months (reductions in MÅDRS scores of 62 and 61%, respectively). In comparative studies with tricyclic or tetracyclic antidepressant agents, the antidepressant efficacy of tianeptine 25 to 50 mg/day (44 to 64% reduction in MÅDRS scores) was equivalent to that of amitriptyline 50 to 100 mg/day for 1 or 1.5 months (53 and 69%), clomipramine 100 to 200 mg/day for 6 months (55%), imipramine 100 to 200 mg/day for 1.5 months (41%) and mianserin 30 to 80 mg/day for 1.5 or 6 months (48 and 50%) in patients with major depression (single episode or recurrent), bipolar disorder (depressed), dysthymic disorder or adjustment disorder. Tianeptine 37.5 mg/day (56% reduction in MÅDRS score) was more effective than maprotiline 75 mg/day for 2 months (47%) in a study of perimenopausal women with anxio-depressive symptoms and less effective than dothiepin 150 to 225 mg/day for 1 month in a small study of patients with depressive disorders. The anxiolytic efficacy of tianeptine was assessed in several comparative trials of patients with concurrent depression and anxiety. Tianeptine 25 to 50 mg/day appears to have equivalent anxiolytic efficacy to fluoxetine 20 mg/day for 1.5 to 3 months, sertraline 50 mg/day for 1.5 months, amitriptyline 50 to 100 mg/day for 1 to 1.5 months, clomipramine 100 to 200 mg/day for 6 months and mianserin 30 to 80 mg/day for 1.5 or 6 months. Superior anxiolytic efficacy was attributed to tianeptine over maprotiline 75 mg/day for 2 months in a study of perimenopausal women with anxio-depressive symptoms. Tianeptine 25 to 50 mg/day is effective as long term treatment to prevent relapse or recurrence in patients with depression. It also appears to have potential for use in specific subgroups. The efficacy of tianeptine 25 or 37.5 mg/day was equivalent to that of mianserin 30 mg/day and similar in some but not all parameters to that of fluoxetine 20 mg/day in elderly patients. Patients with chronic alcoholism often develop depression, especially on withdrawal of alcohol. Assessments of antidepressant and anxiolytic efficacy for tianeptine 37.5 mg/day were equivalent to those for amitriptyline 75 mg/day over 1 to 2 months in this patient population. Improvements in quality-of-life scales with depressed tianeptine recipients were similar to those in patients receiving mianserin or fluoxetine. Tolerability The adverse effect profile of tianeptine appears to be similar in many respects to that of the SSRIs, in that cognitive, cardiovascular and bodyweight effects are minimal in comparison with the classical tricyclic antidepressant agents. In fact, in comparisons with placebo, the only symptom appearing significantly more often with tianeptine was headache. In clinical trials, the most common adverse effects seen in patients with depressive disorders receiving tianeptine were gastrointestinal (nausea, constipation, abdominal pain) or CNS (headache, dizziness, change in dreaming) disturbances, which decreased in frequency with continued treatment. Effects such as dry mouth, hot flushes, somnolence, vertigo, gastrointestinal disturbances, increased bodyweight, increased heart rate and tremor occurred significantly more often in patients receiving tri- or tetracyclic antidepressant agents than in those receiving tianeptine. In studies comparing tianeptine with fluoxetine, paroxetine or sertraline, in contrast, the incidence of most adverse effects was similar; nausea, tremor and palpitations tended to occur more often in fluoxetine recipients, and the incidence of dry mouth tended to be higher in tianeptine recipients. Tianeptine has only rarely been associated with hepatoxicity. The favourable tolerability profile of tianeptine has been confirmed in long term trials, and in elderly patients (including those with cardiovascular pathology before treatment initiation) and patients with alcoholism. The low incidence of anticholinergic and neurological effects associated with tianeptine is of particular importance in these subgroups, who have increased sensitivity to the adverse effects of psychotropic drugs. Tianeptine has a wide therapeutic margin; overdosage has been associated with only minor transient adverse effects. Dosage and Administration The recommended dosage of tianeptine in patients with depression is 37.5 mg/day orally in 3 divided doses, with meals. The dosage should be reduced in elderly patients and patients with severe renal failure, but dosage reduction is not required in patients with chronic alcoholism or hepatic impairment or those undergoing haemodialysis. The dosage of tianeptine should be reduced over 1 to 2 weeks when discontinuing treatment, although there is little evidence of psychological or physical dependence on the drug. As with other antidepressants, tianeptine is contraindicated in patients taking monoamine oxidase inhibitors.