Delusional infestation in the treatment of ADHD with atomoxetine

Abstract

The case describes an adult diagnosed with attention deficit hyperactivity disorder and treated with atomoxetine who quickly developed a florid case of delusional infestation. The patient described very distressing experiences that were significantly impacting her daily life. The symptoms improved with the withdrawal of atomoxetine and resolved completely with antipsychotic medications. Atomoxetine is proposed as the putative causative agent in this case.

Background

Delusional infestation (DI), also known as Ekbom’s syndrome, is a disorder whereby an individual incorrectly believes that they are infested by living or inanimate pathogens despite the absence of any supporting medical evidence.^{1 2} DI can occur as a primary or secondary condition. In the latter, it can be as a result of a number of medical or psychiatric illnesses or due to substance use or prescribed medications. We are unaware of any other reports in which a case of DI is thought to be secondary to atomoxetine treatment. It is therefore of importance and interest to all who may prescribe this medication or treat those with attention deficit hyperactivity disorder (ADHD).

Case presentation

The patient is a 38-year-old, unemployed mother of two. She had been referred to the community mental health team by the child and adolescent psychiatrist treating her daughter for ADHD as it was felt likely that she suffered from this condition also.

A detailed assessment was undertaken over two 60 min appointments, including the use of the diagnostic interview for ADHD in adults (DIVA) and a collateral history obtained from her own mother. This revealed a life-long pattern of physical overactivity, impulsivity, an inability to relax and difficulty in sustaining attention. The patient had little by way of psychiatric history, but at the age of 17 had been referred to mental health services with ‘anger problems’ and had received some cognitive behavioural therapy to this end. She had no significant medical history and was not on any prescribed medication. She gave a family history of depression and ADHD and described past use of cannabis in her 20s, although currently abstinent. There was no family history of any psychotic illness. At the initial appointments, the patient presented as a petite, slim woman with good evidence of self-care. She was fidgety and struggled to sit still but engaged well. She spoke quickly and spontaneously but was euthymic. There was no abnormality of thought or perception or any other identifiable psychopathology.

Ultimately, it was agreed that the patient met diagnostic criteria for adult ADHD, and this was shared with her and her family. She felt that she would like to pursue pharmacotherapy for ADHD and, after lengthy discussion, her preference was to start atomoxetine as opposed to psychostimulant medication to avoid appetite suppression and weight loss side effects. Her weight, blood pressure and heart rate were measured at baseline and were satisfactory. She was therefore commenced on atomoxetine at the recommended initial dose of 20 mg daily (due to her weight of 45 kg) and then increased to 50 mg after 4 weeks having suffered no adverse effects or side effects.

After 6 weeks, at the higher dose of atomoxetine, the patient’s mother contacted the community mental health team (CMHT) with concerns around some newly emergent ‘weird ideas’ and erratic behaviour. The patient had already consulted her general practitioner (GP), who had prescribed diazepam 2 mg as required for the extreme level of distress she displayed. She was reviewed at the CMHT, at which stage she had been taking atomoxetine for a total of 12 weeks. She described the new and distressing conviction that there were ‘black bugs or fibres’ living in her skin. She could feel them crawling in her skin and reported seeing them emerging from the skin of her hands and forearms. She also admitted to trying to ‘pull them out’ by picking at her skin. An examination of her skin revealed no abnormality except for excoriations, and no ‘bugs’ were visible although she reported she could see some. On discussion, the patient attributed this infestation to her home environment, believing that it may have originated from a damp patch in her kitchen. She was hugely distressed and agitated. Indeed, concerns were raised by Ms T’s landlord as she appeared to have made small holes in the walls of a number of rooms apparently attempting to remove ‘bugs’. The patient was informed she was at risk of losing her tenancy. There was no thought disorder, other delusional ideas or hallucinations. She denied substance misuse.

Investigations

Laboratory investigations including a full blood count, electrolytes, liver function tests, inflammatory markers, vitamin B₁₂, folate, ferritin and thyroid tests were within the normal range. A sample of the ‘black bugs’ was analysed by pathology and found to represent ‘vegetable matter’. A skin scraping was negative for fungal infection. A urine drugs screen was negative for heroin, methadone, morphine, codeine, amphetamines, cocaine and cannabis. It was positive for benzodiazepines, which were prescribed by her GP. Furthermore, the patient’s home was investigated by the local environmental health office, and no evidence of any infestation was found.

Differential diagnosis

A number of diagnoses were considered, including a primary psychotic illness or a genuine dermatological condition. However, as a result of the normal examination and negative investigation results, it was agreed DI was the most likely diagnosis. Given the temporal relationship between the onset of symptoms and the prescription of atomoxetine, this was felt to be a possible causal agent.

Treatment

Following the investigations described above, it was agreed to discontinue the prescription for atomoxetine and to observe the patient’s response. After 6 weeks, medication free with careful monitoring, the patient’s presentation had improved markedly, with no other interventions during that timeframe. She did not describe any extension in the infestation and had no new ‘lesions’ but remained convinced that the infestation had occurred and remained significantly troubled by her experience. Given her ongoing levels of distress, psychiatric treatment in the form of olanzapine 5 mg/day was commenced.

Outcome and follow-up

The patient reported no significant side effects from the addition of neuroleptic medication and over the following 8 weeks, the crawling sensations reduced, her belief in the infestation diminished and she became calmer and less distressed.

She was followed-up as an outpatient for a further 6 months at the time of writing. There has been no recurrence of her symptoms.

Discussion

DI is a disorder whereby an individual incorrectly believes that they are infested by living or inanimate pathogens despite no medical evidence to support this.^{1 2} This infestation can take the form of parasites, worms, bugs or other insects living within their body or immediate environment. People with DI commonly report tactile and visual hallucinations that support their beliefs.^{3 4}

The details of DI vary between sufferers, though it typically manifests as a formication that is perceived as parasites crawling on or burrowing into the skin.¹ Individuals often interpret markings on the skin, or small particles found on them or their clothing as evidence of the infestation. The ‘matchbox sign’ describes the frequent presentation of such ‘evidence’ to medical professionals when seeking help.^{1 3}

DI is more common in women and in people over 40 years of age.⁵ It can occur as a primary or secondary disorder due to medical disease, substance use or other psychiatric disorders.⁴

Atomoxetine is a norepinephrine reuptake inhibitor which is approved for the treatment of ADHD in children and adults. Its primary advantage over the standard stimulant treatments is that it has little known abuse potential. It has been found to significantly reduce inattentive and hyperactive symptoms although the responses were lower than the response to stimulants.¹ Common side effects include constipation, dizziness, tachycardia and hypertension.²

Presented here is a case of delusional disorder (manifest as DI) thought to be secondary to the prescription of atomoxetine for adult ADHD. The presence of a clear temporal relationship and the gradual improvement with the withdrawal of the putative causative agent would support this.

Atomoxetine differs from other medications commonly prescribed to treat ADHD in adults and children in that it is the first non-stimulant to obtain a licence to treat these illnesses.⁶ There are numerous reports of psychosis and delusions secondary to treatment of ADHD with stimulants, such as methylphenidate,⁷ but atomoxetine has thought to be safer in this regard. The manufacturers of atomoxetine as Strattera, lilly, list psychosis as a ‘very rare’ side effect.²

On review of the literature, there are very few published cases describing psychotic symptoms in patients prescribed atomoxetine, and to our knowledge, no cases reported of delusional disorder or DI. One review of reports made to the US Food and Drug Administration of adverse effects from atomoxetine in child and adolescents found a total of four patients with psychosis/manic adverse events occurred during 487.5 person years of double-blind treatment with these drugs, and no comparable adverse events occurred in a total of 256 person years of placebo exposure in the same trials.⁸ There was no equivalent study looking at adults prescribed atomoxetine. However, from post-marketing cases reports, as of 30 June 2005, a total of 360 child, adolescent and adult patients receiving atomoxetine reported experiencing psychosis or manic episodes with temporal association to atomoxetine treatment.⁸

The primary action of atomoxetine is on the noradrenergic system as opposed to the dopaminergic one, which is classically most associated with psychosis.⁹ However, some lines of research suggest that noradrenergic signalling plays a causative role in the development of schizophrenia.¹⁰

Olanzapine was chosen to treat the delusional disorders as it is a generally well-tolerated atypical antipsychotic. Several case reports have indicated the beneficial effects of atypical antipsychotics in primary DI, such as risperidone, quetiapine, olanzapine and amisulpride.^11–13 However, the prescription of an antipsychotic could be viewed as a potential weakness of this case, as it is possible that JT’s psychotic symptoms may have completely resolved without treatment having discontinued the presumed causal agent.

Learning points.

• This is the first report describing the onset of delusional infestation following an atomoxetine prescription.

• This case would support previously recorded evidence for the use of atypical antipsychotics in the treatment of this condition.

• This case highlights the need for careful monitoring of patients beginning treatment for attention deficit hyperactivity disorder, including those prescribed non-stimulant preparations.