Duloxetine-Induced Manic Switch in a Patient with Bodily Distress Disorder: A Case Report and Brief Literature Review

INTRODUCTION

Duloxetine is a dual-acting antidepressant (serotonin-norepinephrine reuptake inhibitor or SNRI). It works by blocking the reabsorption of serotonin and norepinephrine, which helps alleviate symptoms of depression and anxiety. It also increases dopamine levels by blocking norepinephrine transporters, which affect both dopamine and norepinephrine.¹ This increase in dopamine mainly occurs in the prefrontal cortex, where dopamine transporters are scarce, and norepinephrine transporters play a bigger role in reabsorption.² Duloxetine is used to manage various types of chronic pain by enhancing the activity of noradrenergic and serotonergic neurons in the spinal pathway.³ Here, we present a case of a duloxetine-induced manic switch. Although there are reports of manic switch in the literature with Duloxetine in the past, to our knowledge, this is the first reported case of switch in a patient with a diagnosis of bodily distress disorder.

CASE REPORT

Our patient, Ms. LB, a 53-year-old female patient, presented to the out patient department (OPD) with symptoms of pain in multiple joints of the body, gradually progressive pain and tingling in the C5 distribution on the right upper limb, sleep disturbance, loss of appetite, menstrual irregularities, intermittent headache, and gastrointestinal (GI) disturbances in the form of “gas” for at last 5–6 years. Family history was positive for primary psychotic illness in a first-degree relative, i.e., in her mother. She was diagnosed with C5 radiculopathy by physicians in the community and has visited many doctors over the past few years but was not satisfied with the treatment. Lastly, there was some relief with 50 mg of Duloxetine and 100 mg of Quetiapine. Along with this medication, she was prescribed a Tablet of Pramipexole 0.5 mg, a Tablet of Metoprolol 25 mg, and a Tablet of Methylcobalamin 1500 mcg. Although she continued the medications for 3 months, she was not entirely satisfied with the consultations. She was referred to the Psychiatry OPD and, on the first visit, was diagnosed to be a case of bodily distress disorder (as per ICD-11). There was no history of any mood episodes in the past. Pramipexole, Metoprolol, and Quetiapine were stopped, and the rest of the medications were continued. Furthermore, she was referred to the Department of Orthopedics for the management of radiculopathy, where no new medication was added, and was asked for follow-up after a month.

She came back for a follow-up after 1 month when she expressed her satisfaction to the fullest, but the interviewer observed that her psychomotor activity and speech productivity had increased significantly; her effect was euphoric with poor insight. Her husband corroborated the findings and further mentioned she is not troubled by lack of sleep anymore, although she is sleeping 3–4 hours every night. The diagnosis was changed to bipolar affective disorder. Young Mania Rating Scale (YMRS)⁴ was applied [Table 1], and the score turned out to be 19. Duloxetine was tapered and stopped, and Lithium was added.

The patient came for follow-up after 10 days. The Serum Lithium level was 0.73 mEq/L. Manic symptoms have subsided. YMRS score has reduced to 2. She was under regular follow-up, and no new episodes appeared within 8 months of follow-up.

DISCUSSION

In existing literature, a manic switch with Duloxetine was seen at a dosage between 40 mg/day and 120 mg/day [Table 2]. In a previous review of four double-blind placebo-controlled studies conducted over 16 countries, 1 out of 958 patients (case population, placebo-955) treated with Duloxetine reported manic symptoms, whereas 2 patients in the placebo group reported have euphoric mood. In the same paper, the authors reviewed 4 more uncontrolled ongoing studies of 1877 patients taking treatment for stress incontinence; 3 of the studies were long-term extensions of the previously mentioned placebo-controlled trial, and 1 uncontrolled study of 658 women. Only 1 patient reported a manic switch, whereas 6 others reported elevated mood. The conclusion from the authors was that Duloxetine is not associated with a manic switch.⁵ Another secondary analysis could only detect 2 patients in hypomania from a pool of 1139 patients treated with Duloxetine.⁶ Results from both studies indicated the rare occurrence of the manic switch with Duloxetine. The last reported cases of such a switch were from one case report of an adolescent girl with ultra-rapid cycling and a case series of 2 patients in 2007.^7,8 We did not come across any similar review or case report for Duloxetine induced mania or hypomania over the last 15 years. Peritogiannis et al reported a case of a 61-years old female, who had a relapse despite regular use of prophylactic SSRI, was started on Duloxetine, which resulted in hypomanic switch within 2 days of intiation of treatment. Symptoms did not resolve only after stopping Duloxetine but after starting an antipsychotic.⁹

Intriguingly, in our case, despite several evaluations conducted by physicians and psychiatrists in the community over the last 3 months, there was no previous diagnosis of a Mood disorder. Although depressive symptoms were present, they never amounted to a diagnosis of a Depressive episode. There was none but one predictor of bipolarity, which is a family history of severe mental illness in a first-degree relative.¹⁰ It is noteworthy that during this period, the patient did not experience a manic switch with Duloxetine, which can be attributed to the protective effect of a concomitant second-generation antipsychotic Quetiapine.

Duloxetine is commonly employed by psychiatrists, physicians, and specialists from various fields to manage neuropathic pain. However, prior to initiating treatment, physicians are advised to diligently identify potential predictors of bipolar illness and remain vigilant for any changes in mood state during follow-up, especially during the early days of the treatment. Such precautionary measures are crucial to ensure optimal patient care and minimize the risk of mood disturbances associated with Duloxetine therapy.

CONCLUSION

This case underscores the need for heightened vigilance when prescribing Duloxetine, particularly in patients with potential bipolar predictors, such as a family history of severe mental illness. While Duloxetine-induced manic switch is rare, this report highlights its possibility even in patients without a prior diagnosis of mood disorders. Physicians should carefully evaluate psychiatric histories, monitor for mood changes during follow-up, and consider protective strategies, such as adjunctive antipsychotics when appropriate. This proactive approach can help mitigate risks and ensure safe and effective treatment outcomes.