INTRODUCTION — Delusional infestation (also called delusional parasitosis [1]) is a rare disorder in which affected individuals have the fixed, false belief (delusion) that they are infected by "bugs": parasites, worms, bacteria, fungi, mites, or other living organisms, or “fibers.” As with all delusions, this belief cannot be corrected by reasoning, persuasion, or logical argument. Many affected individuals are quite functional; for the minority, delusions of parasitic infection may interfere with usual activities, and for some very significantly [2].

Delusional infestation is a delusional disorder of the somatic type [3], a subgroup of delusional disorders in which nonexistent disease or alteration of the body forms the basis of the disorder. Delusions of infestation are the most common form of monosymptomatic hypochondriacal psychosis; others include delusions of dysmorphism and delusions of body odor or halitosis.

This topic addresses the treatment of delusional infestation. The epidemiology, clinical presentation, and diagnosis of delusional infestation are discussed separately. Other psychotic disorders are discussed separately. First- and second-generation antipsychotic drugs are discussed separately. (See "Delusional infestation: Epidemiology, clinical presentation, assessment and diagnosis" and "Postpartum psychosis: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "First-generation antipsychotic medications: Pharmacology, administration, and comparative side effects" and "Second-generation antipsychotic medications: Pharmacology, administration, and side effects" and "Schizophrenia in adults: Maintenance therapy and side effect management".)

TERMINOLOGY — Two forms of delusional infestation are widely recognized [4,5]:

●Primary delusional infestation – Primary delusional infestation is a psychiatric disorder with the delusion of parasitic infection as its only manifestation.

●Secondary delusional infestation – Secondary delusional infestation is a symptom rather than a disorder. The delusion of infestation occurs secondary to another psychiatric disorder or to a medical illness.

APPROACH TO THE PATIENT — Key to the management of patients with delusional infestation is the development of a strong, therapeutic relationship. Many patients express dissatisfaction with previous clinicians whom they believe are incompetent and uncaring. As a result, patients often fail to attend follow-up appointments and receive inadequate or no therapy. A nonjudgmental approach, acknowledgment that the patient's symptoms are real, and empathetic exploration into the effects their symptoms have had on their daily lives can instill a sense of trust [6].

It has been debated whether or not the clinician should overtly agree or disagree with the patient's beliefs [7]. Many authors suggest that a nonconfrontational approach be employed [2,7-9], using phrases such as "I cannot see any parasites today" rather than "there are no parasites" [10], and acknowledging that a problem may have resulted from a previous infection [11]. In our clinical experience, it is important to neither dismiss patients’ complaints as trivial nor to overtly support unfounded beliefs and feed into their delusional system. Reassurance that the patient can be helped can be worthwhile.

Convincing patients to take antipsychotic medications is a major challenge in the management of this disorder. Rejection of a psychiatric basis for the dermopathy is a defining characteristic of the illness, thus rejection of psychiatric treatment is to be expected. A number of strategies have been suggested in prescribing antipsychotics for these patients.

●One strategy is to tell the patient that the problem is a "biochemical imbalance," possibly the result of a previous infection that is no longer present. Patients may be more likely to agree to take medication for treatment of a "chemical imbalance" than for a psychiatric problem.

●It should be explained to the patient that although antipsychotic drugs are commonly used for schizophrenia, it is not being used for schizophrenia and the patient does not have the disorder.

●It can be further explained to the patient that drugs used for one purpose are often found to have additional unrelated uses. It is important to provide examples, such as aspirin for pyrexia and stroke prevention, beta blockers for coronary artery disease and prevention of migraine headaches, or amitriptyline for depression and neuritis.

●Some patients may be persuaded to try medication when told that other patients with a similar condition have experienced great relief in their symptoms.

●For patients who ask why they continue to "see" parasites when others do not, the concept of the "phantom limb" may be presented as a possible explanation.

Some clinicians recommend bypassing the disclosure of a delusional diagnosis to patients who are likely to respond by refusing the antipsychotic, thus protecting them from harm. This approach is controversial; clinicians also raised concerns about withholding information based on principles of patient autonomy and informed consent [12,13].

In the case of initial adverse drug events or failure of an antipsychotic drug, it is helpful to explain to the patient that it is important to find the “right drug for the right patient,” one that is both safe and effective. This explanation may help allay the patient’s concerns or impatience when more than one drug regimen is necessary.

APPROACH TO PHARMACOTHERAPY

New presentation — We recommend first-line treatment of primary delusional infestation with an antipsychotic medication rather than other medications. Systematic reviews and meta-analyses have not found convincing evidence that any antipsychotics are consistently more effective than any others [14-16]. (See 'Efficacy' below.)

In absence of differences in efficacy, we suggest selecting an antipsychotic that has a favorable side effect profile given the individual patient’s clinical presentation. Antipsychotics vary widely in their side effect profiles (table 1). (See 'Side effects' below.)

We favor second-generation antipsychotics rather than first-generation antipsychotics for first-line treatment of delusional infestation based on the generally lower rate of extrapyramidal side effects. (See "Second-generation antipsychotic medications: Pharmacology, administration, and side effects".)

Patients with delusional infestation often respond to antipsychotic drugs at lower doses than patients with other psychotic disorders. The antipsychotic should be initiated at a low dose and increased gradually (eg, in weekly increments) to minimize side effects and arrive at the lowest effective daily dose. After achieving an adequate clinical response, the antipsychotic should be maintained at a therapeutic dose for at least one month, and preferably several months [17,18].

As examples:

●Risperidone can be started at 0.5 mg/day (given as one or two daily doses) and advanced weekly to the lowest clinically effective dose [19-21]. The dose can be increased up to 8 mg/day, though in our experience most patients require between 2 and 4 mg/day.

●Aripiprazole – Starting dose 2 mg, increased by 2 mg every two weeks; typical dose 8 to 12 mg/day.

●Olanzapine – Starting dose 2.5 mg/day; typical dose 2.5 to 7.5 mg/day. However, doses up to 20 mg/day may be necessary in some patients for an optimal response [22-24].

●Quetiapine – Starting dose 25 to 50 mg; typical dose 200 mg daily.

Good response to antipsychotic — When discontinued, the medication should be tapered gradually over a period of weeks [17,18]. If relapse occurs, patients often respond to reinstitution of the drug. Relapses are common though the rate is not known [10]. Some patients require prolonged therapy to avoid relapse.

Poor response to antipsychotic — Adjustments to antipsychotic treatment in cases of poor response are reviewed separately.

ANTIPSYCHOTIC MEDICATION

Efficacy — There are no randomized clinical trials of antipsychotic medication for primary delusional infestation or delusional disorders [25,26]. A review of published case series and observational trials involving approximately 100 patients with primary delusional infestation found response rates for antipsychotics of 60 to 100 percent [25].

In analyses of published outcomes of treated cases of delusional infestation, no particular antipsychotic agent appears clearly superior to others, nor is there a difference in response rates between first- and second-generation antipsychotics (FGAs and SGAs). However, randomized controlled trials comparing antipsychotics for the disorder are lacking.  

●FGAs described in published cases as effectively treating delusional infestation include pimozide [10,27-30], perphenazine [31], chlorpromazine [32], thioridazine [33], trifluoperazine, haloperidol, and fluphenazine [25].

●SGAs described in case reports and case series as effectively treating delusional infestation, including risperidone [19-21,34], olanzapine [35-38], quetiapine [34], sertindole [39], sulpiride [18], aripiprazole [40], paliperidone [39], and ziprasidone [41].

Randomized clinical trials have demonstrated the efficacy of antipsychotics in reducing psychosis in a variety of psychotic disorders [42-44], without consistent differences in efficacy among the medications. (See "Bipolar mania and hypomania in adults: Choosing pharmacotherapy", section on 'Initial treatment' and "Unipolar major depression with psychotic features: Acute treatment", section on 'Treatment' and "Psychosis in adults: Initial management", section on 'Antipsychotic therapy'.)

Pimozide, an FGA that has been widely used in practice and published reports for delusional infestation [10,27-30], is no longer considered first-line treatment. Pimozide has antagonistic effects on opiate receptors in addition to a selective blockade of dopamine type 2 receptors. The opioid blockade has been postulated as contributing to a reduction in pruritus and formication [25,45]. However, there is no rigorous evidence that pimozide is more effective in treating delusion infestation than other antipsychotic drugs [45,46]. In addition, pimozide’s side effect profile has disadvantages compared with other antipsychotics. (See 'Side effects' below.)

Side effects — Common adverse effects of FGAs include extrapyramidal side effects (tremor, bradykinesia, shuffling gait, akathisia), acute dystonic reactions, tardive dyskinesia, and hyperprolactinemia. (See "First-generation antipsychotic medications: Pharmacology, administration, and comparative side effects".)

Pimozide, along with thioridazine and intravenous haloperidol, prolong the QT interval, particularly at higher doses. Sudden death in patients on pimozide has been reported [47], typically with doses of 10 to 20 mg daily. These medications should be avoided in patients with cardiac disease, a history of syncope, a family history of sudden death, elderly patients, and in conjunction with other medications that prolong the QT interval such as antiarrhythmics and erythromycin.

Prior to the use of these medications in eligible patients, serum electrolytes should be measured (and, if abnormal, corrected prior to beginning therapy), and an electrocardiogram should be performed prior to starting pimozide and periodically during treatment [48]. In the absence of more specific guidelines, we perform an electrocardiogram every four to six months, when doses are increased rapidly, or when doses approach or exceed 10 mg daily. Increase of the QT interval by 25 percent or more from baseline, or a QT interval >520 milliseconds, warrant temporary cessation of the drug, followed by dose reduction or change in antipsychotic. (See "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".)

Adverse effects associated with SGAs include metabolic side effects (weight gain, diabetes, hyperlipidemia) QT interval prolongation, akathisia, and tardive dyskinesia. Some of these medications also cause extrapyramidal side effects but generally at rates lower than first-generation agents [14,49,50].

A table provides a recommended schedule for monitoring the metabolic effects of FGAs and SGAs (table 2). More frequent measurements may be necessary for individual patients (eg, more frequent assessment of lipids and glucose in the patient who has a significant weight gain) or for patients on specific antipsychotics (eg, olanzapine and quetiapine), where there is clear evidence of an increased risk of insulin resistance [51].

SECONDARY DELUSIONAL INFESTATION — Treatment of a secondary delusional infestation should focus on the primary medical illness or psychiatric disorder. Antipsychotic drugs are sometimes used symptomatically for limited periods, but play a minor role in treatment unless indicated for treatment of the primary illness. (See "Delusional infestation: Epidemiology, clinical presentation, assessment and diagnosis", section on 'Secondary delusional infestation' and "First-generation antipsychotic medications: Pharmacology, administration, and comparative side effects" and "Second-generation antipsychotic medications: Pharmacology, administration, and side effects".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Psychotic disorders".)

SUMMARY AND RECOMMENDATIONS — Delusional infestation (also called delusional parasitosis [1]) is a rare disorder in which affected individuals have the fixed, false belief (delusion) that they are infected by “bugs”: parasites, worms, bacteria, fungi, mites, or other living organisms, or “fibers.” (See 'Introduction' above.)

●Two forms of delusional infestation have been described.

•Primary delusional infestation is a psychiatric disorder with the delusion of parasitic infection as its only manifestation. It is a diagnosis of exclusion after ruling out a parasitic infection and other medical and psychiatric illnesses. (See "Delusional infestation: Epidemiology, clinical presentation, assessment and diagnosis".)

•Secondary delusional infestation is a symptom of another psychiatric or medical illness rather than a disorder. Treatment is generally focused on the primary disorder. (See "Delusional infestation: Epidemiology, clinical presentation, assessment and diagnosis", section on 'Secondary delusional infestation'.)

●Patients with delusional infestation typically present in primary care or to a dermatologist. They usually are highly resistant to the idea of assessment by a psychiatrist. Whether in general medical care or psychiatric care, the development of a strong, therapeutic relationship instilling trust is central to clinical management. (See 'Approach to the patient' above.)

●Convincing patients to take antipsychotic medications is a major challenge in the management of this disorder. Rejection of a psychiatric basis for the dermopathy is a defining characteristic of the illness, thus rejection of psychiatric treatment is to be expected. (See 'Approach to the patient' above.)

●For patients with primary delusional infestation, we recommend treatment with an antipsychotic medication (Grade 1B). Antipsychotic medications are associated with high treatment response rate; other therapies have not been systematically evaluated. (See 'Approach to pharmacotherapy' above.)

●There is no rigorous evidence that pimozide or any antipsychotic has superior efficacy compared with any other. Pimozide, a first-generation antipsychotic that has been widely used in practice and published reports for delusional infestation, is no longer considered first-line treatment. (See 'Efficacy' above.)

●In absence of differences in efficacy, we suggest selecting an antipsychotic that has a favorable side effect profile given the individual patient’s clinical presentation. Antipsychotics vary widely in their side effect profiles (table 1). (See 'New presentation' above.)

●Patients with delusional infestation often respond to antipsychotic drugs at lower doses than patients with other psychotic disorders. The antipsychotic should be initiated at a low dose and increased gradually (eg, in weekly increments) to minimize side effects and arrive at the lowest effective daily dose. (See 'New presentation' above.)

●After achieving an adequate clinical response, the antipsychotic should be maintained at a therapeutic dose for at least one month, and preferably several months. (See 'Good response to antipsychotic' above.)

●Adjustments to antipsychotic treatment in cases of poor response are reviewed separately.

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Jay Keystone, MD, MSc (CTM), FRCPC (deceased), who contributed to an earlier version of this topic review.