Pheniramine dependence in obsessive-compulsive disorder: A case report

1. Introduction

Pheniramine is an alkyl-amine derivative and is a first-generation antihistaminic drug [1] and is often abused [2,3]. When used alone, it stimulates the central nervous system causing initial euphoria. Histamine is known to inhibit the reward pathway; hence, making antihistaminic drugs highly susceptible to abuse [4,5]. It stimulates dopamine transmission in the ventral tegmental region and imbues sedation when abused with opioids and benzodiazepine [6,7].

Pheniramine is a readily available, over-the-counter (OTC) drug. Healthcare professionals do have a higher abuse liability due to the easier access. Abuse frequently begins as a self-medication measure. Along with the potential anticholinergic side effects, it also lowers the seizure threshold [1,8]. Older age, lower income, tobacco dependence, and depression are some of the risk factors of pheniramine abuse. Pheniramine abuse has been reported in patients with psychiatric illnesses such as depression, hypochondriasis, psychosis, alcohol dependence, adjustment disorder, agoraphobia, avoidant personality disorder, dull-normal intelligence, and social phobia [5,6,8–10].

Described below is the case of a pheniramine-dependent patient, who grapples with predominant obsessive-compulsive disorder (OCD). To the best of our knowledge, pheniramine dependence in a patient with OCD has not been reported to date.

2. Case report

To ensure patient confidentiality and privacy, the subject of this study, from here on, is referred to as Mr. P.

Mr. P is a 37-year-old married man holding down a job at the local tobacco (beedi) factory. His schooling consists of higher secondary education. He is from middle socio-economic status with a rural background. He has been shy from his childhood with a handful of close friends. His father probably had a depressive illness and allegedly committed suicide by overdosing on unknown tablets about 15 years back.

Mr. P started developing repetitive thoughts of contamination at the age of 24. He repeatedly washed hands, 7–8 times at one stretch, about 10 times a day. He spent 2 hours following a rigid and inflexible bathing ritual. He had gotten used to checking on his valuables, repeatedly throughout the day, with obsessive doubts of their misplacement or theft.

He sought professional help in 2018, which is about ten years after the onset of initial symptoms. He had no psychiatric consultations prior to that. We diagnosed him to have mixed OCD as per the International Classification of Diseases-Version 10 (ICD-10). His Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) indicated moderate OCD as he scored a 21 out of a possible 40.

He was prescribed sertraline, 50 mg per day, with exposure response prevention (ERP) sessions. Minimal improvement was observed after the first six sessions of ERP after which he had poor motivation for further continuation. Over the next two years, he failed to respond adequately to sertraline which was tried up to 200 mg/day, and subsequently to Fluvoxamine at 100 mg/day which were all prescribed with benzodiazepines as required.

He developed bouts of anxiety and gradually panic attacks, at times with poor insight into his compulsions. He refused to comply and stopped taking medications as soon as he saw improvement in his anxiety and dysfunctional behaviour.

During one of the follow-up sessions, his wife reported that Mr. P was taking “unknown” tablets and injections. Upon further questioning, Mr. P revealed that he was indeed taking pheniramine, over the counter for the last six months. Pheniramine was initially prescribed by a dermatologist for pruritus.

Mr. P acknowledged taking two tablets per day relaxed him. The tablets consisted of 50 mg pheniramine. Mr. P mentioned that this medication, if taken during the early hours, helped him “get through the day”. Eventually, he increased the dosage to 5 tablets/day, in the morning to experience the same feeling of calmness.

Coincidently, about 4 months back he was informed by a relative, who worked at a pharmacy, that injecting pheniramine would make it act faster. After learning the procedure from him, Mr. P started injecting himself [dose] at the cubital fossa. This started once a week initially, eventually progressing to injecting 45 mg (in 2 ml) pheniramine every two to three days. Mr. P continued to inject himself while orally consumed 250 mg of pheniramine as tablets per day. He confessed to injecting pheniramine when he was alone, at times in the washroom, and eventually disposing the empty vials unnoticed.

He reasoned that pheniramine helped him the most in reducing anxiety. Even more than the prescribed psychiatric medications which included benzodiazepines. Also, pheniramine was cheaper and easily available. Hence, it was more convenient for Mr. P to buy pheniramine tablets and injectables than visiting a professional. Besides, pheniramine cost him less than 30 rupees/week. In contrast to this, fluoxetine 20 mg/day, olanzapine 5 mg/day, and clonazepam 0.5 mg/day, combined, would cost him about Rs 72. Although he visited multiple pharmacy stores to procure the medicines, he felt that the stigma associated with buying psychiatric drugs was not present otherwise. He claimed to feel calmer, have better sleep and even save money.

When his wife found out and objected to this, he stopped using them for about 7 days. Following this, he complained of headache, uneasiness, anxiety, and poor sleep. He was irritable, lethargic, and had tremors on examination. He had strong urges to consume and inject the medication and planned various ways of getting out of the house unnoticed to buy pheniramine. He did not have any symptoms of depression.

During this one month of seeking professional help, his YBOCS had reduced to 15 out of 40. We tried to gradually reduce his pheniramine use, with psychoeducation and also started him on Fluoxetine 20 mg and olanzapine 5 mg combination. Augmentation with olanzapine was chosen for its significant anti-histaminic properties [11].

3. Discussion

This case highlights the susceptibility of those with psychiatric illness to pheniramine abuse and dependence. The psychiatric disorders in which pheniramine abuse has been reported are associated with significant anxiety [6]. Pheniramine and chlorpheniramine have shown to reduce initial anxiety [12]. Also, Pheniramine provides immediate relief to the patient; thus, instigating regular usage. Soon, symptoms of tolerance and withdrawal begin to show [2,13].

Other aspects evident from our case report are the ease of availability of pheniramine, its affordability, and the lack of stigma. As a patient with psychiatric illness, being able to procure a medication without associated stigma may be a novel and rewarding prospect.

Thus, self-medication with easily procured pheniramine seems like a beneficial alternative. Low cost of pheniramine reinforces this behaviour [6,14]. For instance, Mr. P, within a month, had spent twice as much on therapy and professionally prescribed drugs than he had on pheniramine.

Besides, chlorpheniramine and diphenhydramine have shown antidepressant properties in some studies. Chlorpheniramine as compared to amitriptyline and imipramine acts on noradrenergic receptors as well. It has an affinity for dopamine and serotonin transporters in the limbic system [7,15–17]. Pheniramine is less sedative than other first-generation antihistaminic drugs. The overall antidepressant effect of chlorpheniramine may be comparable to escitalopram [16].

We stress that our patient did not use pheniramine due to obsessive thoughts. Its continued use was prompted by the instant relief of anxiety initially and later to relieve withdrawal effects. We need to actively enquire regarding the use of OTC drugs in every patient with chronic psychiatric disorders [1].

In this case, the patient hid his pattern of drug usage from his wife for a long time. He had also learned the procedures for intravenous injections with ease and had not reported any infections.

This case also highlights the importance of the proximity of our patient with health care workers. We raise an important question of whether pheniramine can be used just like benzodiazepines to reduce sudden exacerbation of anxiety as and when required in patients with psychiatric disorders [12,15,16]. Both have significant abuse potentials and risk of overdose. However, pheniramine also poses a significant risk of seizures [1]. So, the pros and cons of pheniramine use to reduce anxiety in psychiatric illnesses could be further assessed.