From medical school, we all know the secret code words: “functional”, “supertentorial”, “idiopathic”, and so forth. These, of course, are some of the ways that physicians may refer to patients for whom they cannot make a definitive diagnosis. Such patients, often labeled “somatisizers”, frequent primary care and specialty care physicians' offices as well as emergency rooms.They present with complaints of a variety of aches and pains, fatigue, insomnia, poor concentration, diarrhea, constipation, etc. Any one of these could be the initial signal of a serious medical problem but for this group of patients nothing can be found on physical examination or laboratory and blood tests.

Depending on the specialty of the physician, somatisizers receive a variety of diagnoses. Neurologists cite tension headache, rheumatologists cite fibromyalgia, internists cite chronic fatigue syndrome, gastroenterologists cite irritable bowel syndrome, and psychiatrists cite depression or an anxiety disorder. With the exception of the latter, no treatment has proven particularly successful, and many of these patients, regardless of the diagnosis, wind up being prescribed antidepressants. Does that mean that all somatisizers are suffering from underlying depression or anxiety? Some insist that is the case, but advocacy groups and many patients themselves resist that classification. Physicians are often afraid to suggest to patients that what they are complaining about is really due to a psychiatric problem, fearful of insulting the person. Some doctors, fearing they might overlook something, send the patient for increasingly sophisticated tests, running up healthcare costs and exposing patients to some risk. Inevitably, a test result comes back on the border of abnormality, thus, creating a reason to push forward with even more tests.

We describe a retrospective case series of three patients, two with bipolar depression and one with unipolar depression. Pramipexole is a Food and Drug Administration-approved antiparkinsonian agent, which, when used to augment antidepressants, would be considered an off-label use and should be discussed with the patient. These patients had robust responses to pramipexole augmentation of their treatment regimen. All three patients had been taking an atypical antipsychotic. The depressive symptoms were evaluated using the Hamilton Rating Scale for Depression.

Somatization disorder, multiple chemical sensitivities, chronic fatigue syndrome, fibromyalgia, Gulf War syndrome, neurasthenia, irritable bowel syndrome, conversion disorder…idiopathies one and all. These syndromes and the many others like them have perhaps one overriding commonality: enormous unexplained heterogeneity. Patients and clinicians gaze into the suffering and impact of these symptoms and see as many potential causes as there are symptom combinations.

Whose explanation is best? When I am speaking with psychiatrists, the notion of somatoform symptoms goes largely unchallenged. When I am with rheumatologists, however, fibromyalgia is anything but a psychiatric problem and certainly not a somatoform disorder. Among my toxicologist colleagues, it is readily accepted that low-tevel toxic exposures could account for many idiopathic “sensitivities.”

But what of the high rate of depression and anxiety disorders we see in these patients?” I sometimes unwisely retort.

“Well, it could be a co-factor or an interaction,” is a common response.

Unshaken, I step further into the abyss: “How, then, do you explain the high rate of adverse childhood experiences among people with idiopathic symptom syndromes?”

The response is swift. “You cannot rule out biased recall. We cannot expect people to remember these things accurately in such a negative state of mind.”

And so it goes. After several of these kinds of conversations, I have finally concluded there is no point in arguing.The debate is largely irreconcilable, a debate that strikingly parallels the conflicts many primary care physicians experience with symptomatic patients. “How is your personal life?” the doctor may ask a symptomatic patient, suspecting a psychosocial explanation.

Many patients who present physical symptoms that their doctors cannot explain by physical disease have persisting symptoms and impairment. An influential view has been that such symptoms are the somatization of emotional distress, but there has also been concern that medical practice contributes to shaping these presentations. Analysis of patients' accounts indicate that they approach these consultations with a sense of being the expert on the nature and reality of their symptoms and, in primary care at least, they seek convincing explanations, engagement, and support.They often describe doctors as doubting that their symptoms are real and as not taking their symptoms seriously. Observational research has demonstrated that patients presenting idiopathic symptoms in primary care generally provide cues to their need for explanation or to psychosocial difficulties. Their doctors tend to provide simple reassurance rather than detailed explanations, and often disregard psychosocial cues. Patients seem to intensify their presentation in consequence, elaborating and extending their accounts of their symptoms, perhaps in the effort to engage their doctors and demonstrate the reality of their symptoms. When doctors propose physical investigation and treatment in response to such escalating presentation, they thereby inadvertently somatize patients' psychological presentation. Consultations, therefore, have elements of contest, whereby patients seek engagement from doctors who seek to disengage. Although provision of a medical label, such as a functional diagnosis, can legitimize patients' complaints and avoid contest, this is at the risk of indicating that medicine can take responsibility for managing the symptoms. More collaborative relationships rely on doctors recognizing patients' authority in knowing about their symptoms, and providing tangible explanations that make sense to the patient and allow them to tolerate or manage the symptoms. Researchers need to study how doctors can best achieve these aims within routine consultations.

Worldwide, patients with common mental disorders, such as depression and anxiety, have a tendency to present first to primary care exhibiting idiopathic physical symptoms. Typically, these symptoms consist of pain and other physical complaints that remain medically unexplained. While in the past, traditional psychopathology emphasized the relevance of somatic presentations for disorders, such as depression, in the last few decades, the “somatic component” has been neglected in the assessment and treatment of psychiatric patients. Medical specialties have come up with a variety of “fashionable” labels to characterize these patients and the new psychiatric nomenclatures, such as the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, attempt to classify these patients into a separate “somatoform disorders” category. These efforts fall short, and revisionists are asking altogether for the elimination of “somatoform disorders” from future nomenclatures.

This review emphasizes the importance of idiopathic physical symptoms to the clinical phenomenology of many psychiatric disorders, offers suggestions to the diagnostic conundrum, and provides some hints for the proper assessment and management of patients with these common syndromes.

Somatic symptoms are common in primary care and clinicians often prescribe antidepressants as adjunctive therapy. There are many possible reasons why this may work, including treating comorbid depression or anxiety, inhibition of ascending pain pathways, inhibition of prefrontal cortical areas that are responsible for “attention” to noxious stimuli, and the direct effects of the medications on the syndrome.There are good theoretical reasons why antidepressants with balanced norepinephrine and serotonin effects may be more effective than those that act predominantly on one pathway, though head-to-head comparisons are lacking. For the 11 painful syndromes review in this article, cognitive-behavioral therapy is most consistently demonstrated to be effective, with various antidepressants having more or less randomized controlled data supporting or refuting effectiveness.This article reviews the randomized controlled trial data for the use of antidepressant and cognitive-behavior therapy for 11 somatic syndromes: irritable bowel syndrome, chronic back pain, headache, fibromyalgia, chronic fatigue syndrome, tinnitus, menopausal symptoms, chronic facial pain, noncardiac chest pain, interstitial cystitis, and chronic pelvic pain. For some syndromes, the data for or against treatment effectiveness is relatively robust, for many, however, the data, one way or the other is scanty.

In recent years, research-methods literature mainly addressing controlled clinical trials has arisen regarding explanatory and pragmatic treatment trials. Explanatory trials tend to examine causal mechanisms and questions of efficacy and value internal validity (creating optimal study conditions) over generalizability (using study results to understand treatment effects in real-life patient populations). In contrast, pragmatictrials value “external relevance” (generalizability) of study results over “internal elegance” so that clinicians and health policymakers can better understand how treatments might impact their patients and policies.This review draws inspiration from these contrasting explanatory and pragmatic perspectives and develops them for clinical and research pertaining to idiopathic physical symptoms and related syndromes (eg, somatization disorder, chronic fatigue syndrome, multiple chemical sensitivities, irritable bowel syndrome). Explanatory and pragmatic perspectives are used to examine these idiopathies with regard to causation, case definition, labels, and treatment. It is concluded that idiopathic symptom syndromes are fundamentally pragmatic clinical and research challenges. For epidemiologic and methodologic reasons, the complex explanations for these syndromes remain largely elusive. Even so, scientific and clinical pragmatism offers the opportunity to reduce disagreement between competing medical disciplines and between clinicians and affected patients with regard to irreconcilable etiologic questions and to remain evidence-based in the care of patients.