Untangling the Web of Comorbid Obsessive-Compulsive Disorder and Medical Illness


OCD symptoms can be quite difficult to recognize. Not understanding what is happening, patients tend to be ashamed and suffer in silence, often resulting in a period of 8 to 10 years of untreated illness and long-term negative outcomes.


The key features of obsessive-compulsive-disorder (OCD) are obsessions and compulsions; in most cases of severe symptomatology, avoidance behaviors also are present. Anxiety is a secondary but very pervasive manifestation of OCD. The onset of OCD is typically in late childhood, early adolescence, or early adulthood. The pathophysiology of OCD is uncertain, largely because of the heterogeneity of manifestations and the high rates of comorbidity (anxiety, depressive or bipolar disorder). Furthermore, OCD symptoms can be quite difficult to recognize; intrusive thoughts and behaviors that are the primary features of the disease are internally driven. Not understanding what is happening, patients tend to be ashamed and suffer in silence, often resulting in a period of 8 to 10 years of untreated illness and long-term negative outcomes.1

First-line treatment of OCD consists of cognitive behavioral therapy with exposure and prevention of response often in combination with selective serotonin reuptake inhibitors plus clomipramine. These treatment approaches usually guarantee symptom reduction and remission in at least 60% to 70% of cases. Quite often, they are used together ab initio if symptoms are mild to moderate. International guidelines suggest the use of pharmacological treatment at maximum tolerated doses for at least 8 to 12 weeks, but clinicians should wait even longer to evaluate the potential improvement of symptoms.

For patients who do not achieve remission after a trial of adequate dosage and duration, a switch to another SSRI or clomipramine is recommended. If there is partial response, consider augmenting with a first-generation (eg, haloperidol) or second-generation antipsychotic (eg, risperidone, aripiprazole, olanzapine).

OCD patients: a healthy population?

According to the National Comorbidity Survey Replication (NCS-R), 68% of patients in the US subjects with a psychiatric disorder have at least one co-occurring general medical condition (GMC). In addition, in those with primarily a GMC, 29% report to have a comorbid psychiatric disorder.2

The medical comorbidity question has been widely examined in patients with schizophrenia or bipolar disorder as well as unipolar depression. Metabolic syndrome (primarily abdominal obesity, dyslipidemia, type II diabetes mellitus) and cardiovascular conditions (primarily hypertension) are the most common co-occurring medical condition, with cumulative incidences at age 47 of 56.2% versus 34.4% in the general population.3

Medical comorbidities in OCD and other anxiety disorders have been insufficiently studied; researchers have only started to pay attention to this in the past few years.4,5 As in other psychiatric disorders, pharmacological treatment and unhealthy lifestyles play a leading role in causing these problems. OCD patients often conduct lonely lives, reduce their physical activity, and engage in drinking or smoking to control their symptoms.

Inherited factors such as hypothalamic pituitary adrenal (HPA) axis dysregulation have been considered for a long time as being responsible for altering metabolic profiles. Although a recent study ruled out shared genetic and environmental factors because family members of patients with OCD had the same metabolic and cardiovascular risk as the general population, patients with OCD have a 45% increased risk for any metabolic or cardiovascular complications.3

Cardiovascular issues and antidepressants

As in patients with OCD, risk of cardiovascular disease is higher in individuals suffering with depression. Some antidepressants, if given at full dose (eg, citalopram), can cause QT prolongation, resulting in an increased risk of arrhythmia. As demonstrated by a recent study, SSRIs would not be associated with an increased risk for arrhythmias, stroke, or transient ischemic attack in adults. Fluoxetine seems to reduce the hazard of a myocardial infraction.6

Altered metabolic profile

Reduced physical activity and unhealthy food consumption determine obesity, which is one of the main risk factors for altered metabolic profiles in psychiatric patients. Apart from lifestyle causes, pharmacological treatments (ie, second-generation antipsychotics, antidepressants with high H1 affinity receptor, and mood stabilizers) are responsible for the weight gain that often reduce treatment adherence and determine relapses. Although they are commonly prescribed, only a few studies examined the relationship between antidepressants and weight change.

Tricyclics can determine weight gain through anticholinergic activity while SSRIs seem to lead to weight loss rather than weight gain, at least at the beginning of treatment. This effect could be due to the first improvement of depressive symptoms as well as the activation of the melanocortin system by an increase in serotonin levels. However, as treatment continues, weight gain is frequently reported.7,8 The reason is mostly unknown and not completely understood; it also could be produced by the physiological return to pre-illness weight, after a long period of appetite loss.

The most common metabolic risk factors are diabetes mellitus and insulin resistance. Chronic stress may result in decreased insulin sensitivity, even when there is no weight gain. It is unclear how it happens, most likely the association is multifactorial. A dysfunctional HPA axis may have a role on two levels:

1. At a behavioral level altered appetite, sleep disturbances and reduced activity may result in impaired glucose metabolism.

2. At a molecular level, neuroendocrine and inflammatory responses could develop diabetes mellitus.

Dyslipidemia is another important risk factor that contributes to mortality and morbidity in OCD patients. Relevant associations were discovered relating to the use of SSRIs and higher cholesterol level, increased triglyceride, and reduced high-density lipoprotein cholesterol (HDL-c). Second-generation antipsychotics also make a significant impact on eating behaviors and energy balance. Metabolism centers located in the central nervous system (CNS) balance the need for energy and the seeking of reward. At the peripheral level, all is ruled by connections between muscles, liver, pancreas, adipose tissue, and neuroendocrine organs. Neurotransmitter receptors, the main target of antipsychotic drugs, play a fundamental role in metabolism regulation. Bullet-receptor interaction can both protect and harm metabolism. Different second-generation antipsychotics can (at different levels) determine diabetes, obesity, and lipid profile alterations; pharmacodynamic profiles can only partially explain this difference.9

Plot twist: are therapies the main problem?

A recent Swedish population-based study showed unexpected results: a higher dose of SSRIs and longer treatment duration were correlated with a lower risk of metabolic or cardiovascular problems. This evidence can be explained in many ways, including better disease control, appropriate pharmacological treatment, and unhealthy habits (smoking, unhealthy diet). Full doses of SSRIs could prevent secondary depression; comorbidity can be as high as 80%, but most prevalence rates are around 25% and 50%, considering OCD. Moreover, better symptom control could reduce anxiety, which plays a key role in causing metabolic and cardiovascular alterations.3

Both depression and OCD have an impact on glycemic control, which is exacerbated with high anxiety with consequent hyperglycemia via activation of autonomic responses and triggering the HPA axis. Hyperglycemia can also lead to anxiety in different ways. By increasing cortisol secretion, altering heart rate, and modifying skin conductance levels it can lead to stress-like arousal patterns pervasive in psychiatric patients.10

Patients affected by diabetes mellitus type II, if not well informed on their condition and not trained to deal with it, can develop secondary OCD. They may become obsessed by glycemic control, run unnecessarily frequent blood tests, and live with exaggerated concerns about the condition. Too many alterations of insulin doses can lead to even poorer glycemic control and higher manifestations of OC symptoms.11

Physical well-being results in better quality of life and is associated with lower anxiety levels lowering the risk of a diabetes diagnosis. Mental well-being is linked to lower anxiety and depression, but not to metabolic disease duration or control. Planning psychological intervention for diabetes patients that are targeted on psychological health can result in better self-management and better health outcomes.

When comorbidity occurs, the impairment caused by the psychiatric disease reduces the ability to deal with the medical condition. Deficits in frontal-striatal function have been seen with OCD.12 The integrity of these structures and their connections play a key role in the affective, cognitive, and motor flexibility needed for actions that are goal-directed. Therefore, for OCD patients it could be much more difficult to focus on necessary behaviors to control the metabolic symptoms.13


Patients with OCD as well as those affected by bipolar disorder and schizophrenia have an increased risk for comorbid medical illness. The presence of medical illness is probably multifactorial and can lead to a longer duration of untreated illness with a negative impact on the course of illness. Clinicians should keep in mind that the primary aim should always be to achieve symptom remission as the minimum effective dosage. Moreover, assessing the risk to benefit ratio in treatment planning will help in decision making for the best therapeutic strategies, resulting in reduced risk for relapse, better symptom control, and fewer adverse effects.



Dr Aguglia is Researcher and Psychiatrist, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Dr Giacominiis Resident in Psychiatry, DINOGMI, Section of Psychiatry, University of Genoa, and IRCCS Ospedale Policlinico San Martino; Dr Amerio is Researcher and Psychiatrist DINOGMI, Section of Psychiatry, University of Genoa; IRCCS Ospedale Policlinico San Martino; and Mood Disorders Program, Tufts Medical Center, Boston, MA. Dr Serafini is Associate Professor, DINOGMI, Section of Psychiatry, University of Genoa, and IRCCS Ospedale Policlinico San Martino. Dr Amore is Full Professor, DINOGMI, Section of Psychiatry, University of Genoa, and IRCCS Ospedale Policlinico San Martino. The authors report no conflicts of interest concerning the subject matter of this article.


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