Antidepressants and Somatic Symptoms: Therapeutic Actions Are Expanding Beyond Affective Spectrum Disorders to Functional Somatic Syndromes

B R A I N S T O R M S Clinical Neuroscience Update

Stephen M. Stahl, M.D., Ph.D.

Issue: Having expanded their original role as primary treatment for depression to preferred treatment for anxiety disorders, antidepressants are now emerging as potential therapeutic agents for many other disorders characterized by distressing or even painful somatic symptoms.

Antidepressant Uses: Numerous conditions that have a common causal factor in each of The Emerging Frontier high comorbidity with depression but these conditions. That factor might be The expanded use of antidepres- are themselves characterized by abnormally functioning neuronal cir- sants beyond the treatment of major prominent somatic symptoms may cuits that are regulated by serotonin depressive disorder (MDD) to numer- also be treated effectively with antide- (5-HT) and/or norepinephrine (NE). ous additional affective and anxiety pressants. The frontier for yet further Circuits in one part of the CNS may disorders is one of the remarkable therapeutic uses of antidepressants mediate symptoms of sadness and de- therapeutic advances in psychiatry of has thus shifted from depression and pressed mood,7 and in another, anxiety the past decade. Thus, numerous anti- anxiety to illnesses considered either and fear,8 and in still other areas, dif- depressants now have proven efficacy to be components of an affective fuse and often painful somatic com- in premenstrual dysphoric disorder, spectrum disorder (Table 1)1,2 or to be plaints.9 Boosting 5-HT and/or NE bulimia, panic disorder, generalized members of a category known as neurotransmission in one circuit may anxiety disorder, social anxiety disor- “functional somatic syndromes” reduce sadness, and in another circuit, der, posttraumatic stress disorder, and (Table 2).3,4 Prominent conditions somatic symptoms.7 obsessive-compulsive disorder (Table with encouraging new findings sug- In MDD, some patients may expe- 1). This expansion appears not yet to gesting efficacy of antidepressants in- rience improvement of their sadness be complete, and another remarkable clude not only fibromyalgia5 and and depressed mood, but not their therapeutic advance in psychiatry irritable bowel syndrome,6 but also a somatic symptoms, while taking an may be in the offing for the coming variety of chronic pain conditions.3,4 antidepressant. These individuals are decade. not in full remission. Increasing atten- Do Conditions That Respond to the Same tion is being paid to recognizing and Drugs Have the Same Pathophysiology? treating those with depression who It is plausible that conditions that experience less than full remission of BRAINSTORMS is a monthly section of The Journal of Clinical Psychiatry aimed at providing respond to numerous classes of anti- symptoms, which has led recently to updates of novel concepts emerging from the depressants may share a common a much-enhanced appreciation of just neurosciences that have relevance to the causal factor.1 This does not necessar- how common yet frequently neglected practicing psychiatrist. From the Neuroscience Education Institute in ily mean that depression causes these somatic symptoms are in mood and Carlsbad, Calif., and the Department of conditions (listed in Tables 1 and 2), anxiety disorders.9Ð14 Targeting both Psychiatry at the University of California San Diego. but it does imply that boosting seroto- 5-HT and NE in neuronal circuits that Reprint requests to: Stephen M. Stahl, M.D., nergic neurotransmission, noradren- mediate somatic symptoms is the Ph.D., Editor, BRAINSTORMS, Neuroscience ergic neurotransmission, or both with therapeutic strategy most widely Education Institute, 5857 Owens Street, Ste. 102, Carlsbad, CA 92009. an antidepressant may compensate for employed to reduce these somatic

Table 1. Affective Spectrum Disorder Table 2. Functional Somatic Syndrome Mood disorders Take-Home Points Conditions with prominent painful Major depressive disorder ◆ somatic symptoms Dysthymic disorder All known antidepressants act upon Fibromyalgia Premenstrual dysphoric disorder monoamine neurotransmitter systems, Chronic cervical or lumbar back pain Anxiety disorders usually by inhibiting a presynaptic Irritable bowel syndrome Generalized anxiety disorder transporter often called a reuptake Temporomandibular joint syndrome Panic disorder pump. This psychopharmacologic Interstitial cystitis/female urethral Obsessive-compulsive disorder action has resulted not only in effective syndrome/vulvodynia Posttraumatic stress disorder Primary dysmenorrhea Social phobia/social anxiety antidepressants but also broadly useful Regional musculoskeletal pain/ disorder anxiolytics across a spectrum of myofascial pain syndrome Painful somatic disorders affective and anxiety disorders. Chronic tension headache Fibromyalgia ◆ Patients who suffer primarily from an Non-cardiac chest pain Irritable bowel syndrome affective or anxiety disorder commonly Burning mouth syndrome Migraine Conditions with distressful and often vague Others experience somatic symptoms that are somatic symptoms Attention-deficit/hyperactivity distressing or even painful and which Chronic fatigue syndrome disorder must be eliminated by antidepressant Somatoform disorder Bulimia nervosa treatment for full remission of the Multiple chemical sensitivity Cataplexy affective or anxiety disorder to occur. Exposure syndromes (Gulf War illnesses; “sick-building syndrome”) ◆ A very high number of patients suffer from distressing or even painful somatic symptoms in depression and thus re- symptoms that are not recognized as 4. Katon W, Sullivan M, Walker E. Medical sult in more remission.7 part of an affective or anxiety disorder symptoms without identified pathology: rela- but are increasingly being shown tionship to psychiatric disorders, childhood and adult trauma, and personality traits. Ann Intern Treating Somatic Symptoms nevertheless to respond to treatment with antidepressants. This treatment Med 2001;134(9, pt 2):917Ð925 When the Patient Is Not Depressed response represents a potential 5. Stahl SM. Fibromyalgia: the enigma and the Although the actions of antide- stigma [BRAINSTORMS]. J Clin Psychiatry 2001; opportunity to expand the vistas of 62:501Ð502 pressants on somatic symptoms in antidepressant therapy to a wider range 6. Stahl SM. Gut feelings about irritable bowel MDD are becoming widely recog- of functional somatic syndromes. syndrome [BRAINSTORMS]. J Clin Psychiatry nized,7 it is only now becoming ap- 2001;62:590Ð591 7. Stahl SM. The psychopharmacology of painful parent that conditions with somatic physical symptoms in depression [BRAIN- symptoms but without sadness or burden in functional somatic syn- STORMS]. J Clin Psychiatry 2002;63:273Ð274 depressed mood (Table 2) may also dromes.5,6 Validating the usefulness of 8.Stahl SM. Independent actions on fear circuits may lead to therapeutic synergy for be treated by these same agents, es- antidepressants in functional somatic anxiety when combining serotonergic and pecially those with dual 5-HT/NE syndromes could lead to fulfilling GABAergic agents [BRAINSTORMS]. J Clin Psy- actions. a significant unmet need for disorders chiatry 2002;63:854Ð855 that are very common yet have no 9.Stahl SM. Does depression hurt? [BRAIN- If the brain circuits that mediate STORMS] J Clin Psychiatry 2002;63:382Ð383 somatic symptoms in these condi- currently approved treatments and 10. Simon GE, VonKorff M, Piccinelli M, et al. An tions overlap with those that mediate would usher in an entirely new era international study of the relation between somatic symptoms and depression. N Engl J somatic symptoms in MDD yet are for therapeutic applications of antide- Med 1999;99:1329Ð1335 independent of the brain circuits that pressants. ◆ 11.Kirmayer LJ, Robbins JM, Dworkind M, mediate sadness and depressed et al. Somatization and the recognition of depresssion and anxiety in primary care. mood, it would not be necessary for Am J Psychiatry 1993;150:734Ð741 sadness to be present in order for an- REFERENCES 12. Wu LR, Parkerson GR Jr, Doraiswamy PM. tidepressants to be therapeutic for Health perception, pain, and disability as corre- 1. Hudson JL, Pope HG. Affective spectrum dis- lates of anxiety and depression symptoms in such somatic symptoms. Although order: does antidepressant response identify a primary care patients. 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