Withdrawal Emergent Recurrent Manic Episodes with Use of "Bhukki": A Case Report.

Evidence suggests a strong association between all mood disorders and substance use disorders. This association has been reported to be threefold to fourfold higher for opioid use disorders compared to other substances. Both opioids-induced and withdrawal emergent mania are not reported frequently and, therefore, less understood. While the opioid most commonly related to induced mania is tramadol,[2, 3] withdrawal emergent mania has been mostly reported with opium.[4, 5] Here, we report the case of a young male with recurrent withdrawal associated manic episodes with the use of poppy husk (locally called “bhukki”) who presented to a tertiary care center of central India.

Case Report

A 35-year-old male from rural Chhattisgarh, working as a truck driver, presented with a history of intake of “bhukki” for eight years, taking approximately 30 gm per intake, 3–4 times daily, as a suspension in water. Occasionally he used alprazolam 0.5 mg tablets, 8–10 per day, when he was unable to procure poppy husk. He was reported to be aggressive for the last five days, talking more than usual and sharing elaborate plans of earning a huge amount of money. He could hear the voices of gods and claimed he has been bestowed with their powers. He spent most of the day meeting people, mostly strangers, to share his plans and abilities. He was suspicious of his neighbors, stating that they are conspiring to harm him and his family.

These symptoms appeared after abrupt discontinuation of poppy husk consumption. He reported to have not consumed any benzodiazepines in the preceding two months. There was a past history of similar episodes, which appeared after discontinuing “bhukki,” at least twice in the last three years, and the symptoms had resolved within a few days of commencing treatment.

On examination, he was agitated and uncooperative. He was well oriented, restless, and sweating. Piloerection was observed, and the pupils were dilated and reactive to light (score on the Clinical Opiate Withdrawal Scale [COWS] is provided in Table 1). His speech was pressured and the affect was elated. Delusions of grandiosity and persecution were established; second-person auditory hallucination was also noted. Urine screen for drugs was positive for opioids and negative for benzodiazepines and tetrahydrocannabinol. Other hematological investigations were within normal limits. He was diagnosed as having opioids-dependence syndrome, with harmful use of sedatives or hypnotics, uncomplicated withdrawal state, and withdrawal emergent mania with psychotic symptoms.

Table 1.

Severity Score in COWS and YMRS

Day	COWS Score	YMRS Score
Day 1	14	37
Day 2	5	27
Day 3	1	10
Day 4	0	3
Day 5	0	3

COWS: Clinical Opiate Withdrawal Scale, YMRS: Young Mania Rating Scale.

The patient was admitted for further observation and management. Inj. lorazepam 4 mg IM/IV PRN was advised for managing aggression. Opioid substitution therapy was started with buprenorphine and naloxone fixed-dose combination to manage withdrawal, which subsided at a dose of 4 mg of buprenorphine. Over the next five days, the patient showed significant improvement (COWS and Young Mania Rating Scale scores are given in Table 1). Given the long duration of intake of opioids, high-risk profile, multiple failed attempts, and poor motivation to quit, it was decided to continue oral substitution therapy. He was discharged in a week, for further management on an outpatient basis.

Discussion

Opioid agonists and antagonists have been studied for their psychomimetic effects and mood-altering properties. Among the four receptors of the opioidergic system (i.e., mu, delta, kappa, and nociceptin orphanin FQ peptide), actions through mu and kappa receptors have been implicated in mood alteration. While mu agonism is implicated in tramadol-induced mania,[2, 3] kappa agonism also has been reported to have a rapid onset and transient antimanic property. Moreover, buprenorphine, a kappa antagonist and partial mu agonist, may exert an antipsychotic effect through kappa antagonism. The antipsychotic effect of buprenorphine is also supported by an anecdotal report of psychosis associated with buprenorphine withdrawal.

Apart from these effects, the role of endogenous opioids in mood stabilization has also been highlighted. Pertinently, opioid-withdrawal-led mood destabilization has been implicated in the mania emergent upon withdrawal, especially of opium. Our case confers such mood-stabilizing properties to poppy husk also, whose withdrawal precipitated manic episode. Abrupt discontinuation of even milder opioids, when used in dependence pattern for long periods, can precipitate mania. These emergent manic symptoms are pharmacodynamically analogous to psychosis seen with discontinuation of antipsychotics, which is attributed to super-sensitivity of dopaminergic receptors. Furthermore, our case supports such properties of buprenorphine, which not only was successful as a substitution therapy for poppy husk withdrawal but also aided in remission of manic syndrome.

Alternatively, recurrent emergence of short-lasting episodes of manic symptoms and withdrawal of opioid acting as stressor precipitating underlying bipolar disorder may also be hypothesized in the index case.

In patients presenting with manic symptoms and history of opioid use, clinicians should consider the possibility of withdrawal emergent manic symptoms, which might rapidly resolve with opioid substitution alone.