A 67-year-old woman was referred to the geriatric psychiatric ward complaining of depressed mood, anhedonia, nervousness, brain chirping, fatigue, suicidal ideation, decreased appetite and poor sleep starting 5 months after contracting coronavirus disease 2019. She had intermittent depression for more than 31 years, with one to two episodes per year, each lasting about one month. She had regular outpatient visits and took medicine according to the doctor’s instructions. During this period, there were two severe episodes, one in September 2014 due to a long journey, and the other (this episode) in December 2022 after contracting coronavirus disease 2019. The patient responded well to citalopram, escitalopram (maximum daily dose of 20 mg), and duloxetine (maximum daily dose of 60 mg) while intolerant to venlafaxine, bupropion and trazodone. Her mother was diagnosed with mania. The patient had no history of iron deficiency anaemia, hypothyroidism, or other medical conditions and had no history of any psychoactive substance abuse. No obvious abnormalities were found upon physical or neurologic examination or laboratory tests. She was diagnosed with recurrent depressive disorder and received escitalopram 15 mg/d with no obvious effect over 15 weeks of regular administration, followed by 2 weeks of combined use of duloxetine 60 mg/d as an outpatient therapy, which was less effective. Therefore, we reduced the dose of escitalopram to 10 mg/d and increased the dose of duloxetine to 80 mg/d on admission. Clonazepam at an initial dose of 1.5 mg/d was given to promote sleep. On the morning of the third day, the patient reported itching and creeping sensations deep inside her bilateral shoulders and arms before bedtime, with some remission after moving, which had never happened before. A gradual improvement in mood was reached, but a lack of energy persisted. Thus, escitalopram was discontinued, and duloxetine was increased to 100 mg/d on the sixth day. One week later, the patient exhibited continuous itching and creeping, which caused significant disturbances in sleep at night and drowsiness in the morning. Duloxetine was decreased to 90 mg/d, and clonazepam was concomitantly decreased to 0.5 mg/d for the unrelieved paraesthesia. However, the feeling of creep still held. By clarifying the history, we learned that the patient had a history of intermittent leg soreness since age 41, which increased at rest and decreased after stretching, 3–4 times a week, lasting for half an hour to 4 hours each day, and typically occurred in the evening; however, the patient had never been diagnosed with RLS and had not received specific treatment. The total International Restless Legs Study Group Severity Rating Scale score was 25, indicating severe RLS. None of her first-degree family members reported any previous history of RLS. To consolidate the condition, pramipexole 0.125 mg/d was prescribed to relieve the unpleasant sensations, the dose of duloxetine kept the same. The next morning, the patient reported good sleep without any paraesthesia. She experienced a burning stomach after taking pramipexole, which was relieved by vitamin B6, and this sensation disappeared 3 days later. Polysomnography suggested prolonged sleep latency (34.5 min), poor sleep continuity (27 wake times), deep sleep loss (no N3), low sleep efficiency (80.8%), moderate obstructive sleep apnea hypopnea (apnea hypopnea index = 20.3/hour), multiple transient mentalis myoelectric activities in rapid eye movement sleep, and a periodic leg movement index of 3.6/hour during sleep (Table
1 and
2). After five days, an attempt was made to increase the dose of duloxetine to 120 mg/d to improve energy because of insufficient efficacy at a dose of 90 mg/d. Moreover, we stopped pramipexole to determine whether the discomfort worsened. Not surprisingly, she experienced recurrence of unpleasant sensations in her arms. In the next 3 days, the dose of duloxetine was tapered to 30 mg/d, after which the symptoms disappeared. After consultation with the patient, we ultimately prescribed 40 mg/d duloxetine and 0.125 mg/d pramipexole to balance the efficacy and adverse effects (Fig.
1). Since the patient had difficulty falling and maintaining asleep, trazodone 25 mg/d and clonazepam 1.0 mg/d were added. When her mood and sleep stabilized, clonazepam was gradually discontinued after discharge. She reported complete remission of depression and RLS. Over the 6 months of follow-up, the patient comes to the outpatient clinic every month and takes medicine regularly. Her mood remained stable, and no RLS or RAS reappeared. Pramipexole was discontinued to prevent long-term treatment-induced worsening of RLS symptoms. The patient is still undergoing regular outpatient visits.