Misdiagnosis of serotonin syndrome as fibromyalgia and the role of physical therapists

Physical Therapy, June, 2008 by Gregory M. Alnwick

For physical therapists to become more autonomous practitioners and to meet the American Physical Therapy Association goal of Vision 2020, (1) careful examination and evaluation procedures must be used to question the referral diagnosis rather than to blindly proceed with treatment for fibromyalgia and other disorders of the neuromuscular and musculoskeletal systems. As explained in the Guide to Physical Therapist Practice, (1) physical therapists should engage in an examination process that includes taking a history, conducting a systems review, and performing tests and measures to identify potential and existing problems. (1) Throughout the examination, data are gathered to evaluate and to form clinical judgments. (2) These judgments may consist of formulating a treatment plan or suggesting referral to the proper medical care provider.

As physical therapists conduct their assessments, it is critical to investigate the presence of any signs or symptoms that may indicate the need for referral to the most appropriate health care professional. It is especially important to obtain a detailed history from any patient with a diagnosis of fibromyalgia, a syndrome of unknown etiology that is characterized by chronic widespread joint and muscle pain, (3) or other chronic pain syndromes. If a detailed history is not obtained, then significant information, including medications, may be omitted, increasing the chances of misdiagnosis and inappropriate treatment.

With the increased use of serotonergic medications, a condition triggered by serotonin excess within the brain and spinal cord has emerged and may be gaining prevalence. (4) Selective serotonin reuptake inhibitors (SSRIs), including citalopram, are used to treat depression. Although the exact mechanism of action of SSRIs is not fully understood, it is believed that they inhibit the reuptake of serotonin at the neuronal synapse. (5) Citalopram was approved by the US Food and Drug Administration for the treatment of depression in adults in July 1998. It is administered orally, and peak concentrations in plasma are attained about 4 hours after dosing. Its half-life in an individual who is healthy is 35 hours. Indications for this medication include anxiety, depression, panic disorder, and posttraumatic stress disorder. Some contraindications are abrupt discontinuation, bipolar disorder, bleeding, use in children, driving or operating machinery, mania, and seizure disorders; a more extensive list of contraindications and reasons for precaution is shown in Appendix 1. Adverse reactions to citalopram (5) are shown in Appendix 2. The use of SSRIs for the treatment of various psychiatric disorders is increasing; consequently, the incidence of reported side effects, such as extra-pyramidal movement disorders like those seen in serotonin syndrome (SS), also is increasing. (6)

In order to comprehend SS, it is necessary to have an understanding of serotonin. The actions of serotonin in the peripheral nervous system include vasoconstriction via smooth muscle stimulation, platelet aggregation, uterine contraction, intestinal peristalsis, and bronchoconstriction. In the central nervous system, serotonin has effects on controlled behavior, attention, affect, pain perception, aggression, motor control, temperature control, sleep, appetite, and sexual function. Because serotonin is unable to cross the blood-brain barrier, it must be produced both centrally, within the brain stem, and peripherally, within the intestine. (4)

Serotonin syndrome is an iatrogenic disorder induced by pharmacologic treatment with serotonergic agents that increase serotonin activity. (4,7) It is thought to occur as a result of excess stimulation of the 5-hydroxytryptamine 1A (5-[HT.sub.1A]) receptor and possibly the 5-hydroxytryptamine 2 ([5-HT.sub.2]) receptor. (8-11) Serotonin syndrome may result from an excess of synaptic serotonin following the use of serotonergic agents alone or in combination with other serotonin-enhancing drugs. (6) In most cases, SS has a rapid onset, within minutes to hours, although it can occur over a period of days, weeks, or even months after the start of treatment with various SSRIs. (4,12) The incidence of SS is, in large part, unknown. The variable and nonspecific nature of its presentation makes it difficult to diagnose; therefore, it has gone underreported. (8) Signs and symptoms of SS may consist of mental status changes, with acute manifestations consisting of cognitive behavioral changes, neuromuscular excitability, autonomic instability, and pain. (4,8) Serotonin syndrome also appears to be dose related, with the dose of the medication affecting both the likelihood of developing SS and the severity of the clinical presentation. (4,12,13) Because the signs and symptoms may overlap those of other chronic pain syndromes, a diagnosis is made on clinical grounds. (4)

Serotonin syndrome is not detected by laboratory tests or diagnostic imaging. Sternbach (14) has set forth diagnostic criteria for this syndrome: