Urgent release of severe psychomotor retardation with intramuscular lorazepam: a case report

Introduction

Psychomotor retardation (PMR) is a possible feature of a melancholic depressive episode. It can include slowing of speech, thinking and body movements. Speech may also be decreased in volume or inflection, and there may be increased pauses to the extreme of mutism, which is also a symptom of catatonia.¹ Such individuals may cease eating and drinking fluids, which may place them at risk for deep venous thrombosis (DVT).²

Researchers of PMR in depression have discussed how the antidepressant venlafaxine and repetitive transcranial magnetic stimulation (TMS) both take 3 weeks to lead to improvement.^3,4 Oral lorazepam was used to alleviate mutism in six women, but they quickly relapsed to mutism within hours, and lorazepam did not return them to conversing again.⁵ A crossover study compared oral lorazepam with oxazepam in improving severe PMR, but improvement waned at day 3 of treatment.⁶ A review of the literature did not yield a case in which intramuscular (IM) lorazepam was utilized to urgently treat PMR.

A single photon emission tomography study of akinetic patients with a psychomotor syndrome demonstrated a decrease of GABA-A receptors in the primary motor cortex.⁷ Reduced GABAergic tone may be the cause of the reduction of intracortical inhibition observed in patients with depression in TMS studies.⁸ Lorazepam is a GABA-A receptor agonist that, when administered parenterally, reverses 60–80% of all acute catatonia within 24 h, and in some cases within 5–10 min.⁹ In the present case report, we propose that severe PMR in a hospitalized patient was released with IM lorazepam by increasing GABAergic tone.

Case presentation

A 53-year-old divorced White male with a history of bipolar I disorder was admitted after a suicide attempt via overdose on zolpidem and ibuprofen. He was in a severe melancholic episode of depression with psychotic features, with a 21-item Hamilton Rating Scale for Depression (HAM-D) score of 48 and a Montgomery–Asberg Depression Rating Scale (MADRS) score of 52.^10,11 He had experienced suicidal ideation over the preceding 8 days, with thoughts of dying by carbon monoxide poisoning or hanging. He was evicted from his apartment 2 days prior to admission after verbally threatening neighbors for not assisting him with food or money. He then moved in with his mother, who stated that he had never been one to pity himself. He had also experienced anhedonia for 2 months. For 3–4 weeks prior to admission, he experienced severe depression, feeling hopeless, worthless and guilty. He was worried about finances, and reported sleeping only 2 h per night and feeling lethargic with low motivation, having not showered in days. The patient described auditory hallucinations of video game music for the past week. He had a poor appetite, which was validated by a 6-kg weight loss since his initial hospitalization 2 months earlier, when he was diagnosed with bipolar mania with psychosis. He had displayed 2 weeks of manic symptoms, appearing euphoric and grandiose. This transitioned to hyperirritability and assaultiveness, and he was treated with lithium (1350 mg/day) and olanzapine (10 mg/day) during a 20-day hospitalization. Although he felt that his mood was ‘good, okay’ at the end of that hospitalization, he stopped taking these medications shortly after discharge, as he disagreed with his diagnosis of bipolar disorder.

On mental status examination, the patient had poor eye contact and was clothed only in his underwear. He was tearful throughout the interview, displayed an overall decrease in spontaneous movement, and his speech was monotonous and barely audible, with a 10-s delay in latency when answering open-ended questions. The patient had difficulty generating answers if not repeatedly prompted with yes/no questions. He knew only the month and the year, but not the date, and was unable to check off selections on his menu. He was somatically preoccupied with body aches and seemed to be responding to internal stimuli, moving his lips and mumbling words.

The patient displayed only two Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition¹ symptoms of catatonia: mutism and PMR, approaching stupor. Adding the behaviors of refusing to eat and poor eye contact, which fall under the category of withdrawal, gave him a score of 3 on the Bush–Francis Catatonia Rating Scale, which is below the range of scores of catatonic patients in three catatonia studies.¹² An inventory of his motor and cognitive symptoms gave him a very high Salpêtrière Retardation Rating Scale score of 51 (maximum 60).¹³

Urine drug screen did not detect amphetamines, barbiturates, benzodiazepines, buprenorphine, cannabinoid, cocaine, ecstasy, methadone, opiates or oxycodone. Blood test results were as follows: white blood cell, 7500 per µl; hemoglobin, 15.4 g/dl; hematocrit, 45.7%; aspartate aminotransferase, 22 IU/l; alanine aminotransferase, 20 IU/l; sodium, 137 mmol/l; potassium, 3.8 mmol/l; chloride, 105 mmol/l; CO₂, 27 mmol/l; glucose 132 mg/dl; blood urea nitrogen, 13 mg/dl; creatinine, 1.0 mg/dl; thyroid stimulating hormone, 0.59 mIU/ml. The patient was not drinking fluids or eating food from his meal trays, and we were concerned that he was at risk for dehydration and/or DVT.

We were concerned that the patient’s PMR would progress to catatonia, as this is a possible manifestation of bipolar disorder.¹ With his consent, we administered lorazepam 2 mg IM on the second day of his hospitalization, with the aim of reversing the PMR. He had not received any other psychotropic medications prior to this. Within 1 h of receiving lorazepam, he became more spontaneous and interactive, and asked to shower and shave. He walked out of his room to retrieve his dinner, and telephoned his mother to request that she visit. Within 24 h of his first injection of lorazepam, his Salpêtrière Retardation Rating Scale score improved to 15. On hospital day 3, the patient declared that the intense dysphoria had improved. He recalled that, prior to receiving lorazepam, he experienced racing thoughts of negativity and was unable to express them or divert his attention away from them. After receiving lorazepam, he felt relaxed but still depressed. Because the patient still had a monotonous and soft voice, he was prescribed oral lorazepam 1 mg twice daily for 5 days, and lithium was initiated at 1350 mg/day 1 h after IM lorazepam was given in order to mitigate his depression and improve his concentration. He still complained of fleeting suicidal ideation, anxiety, insomnia, poor concentration and low motivation, so extended-release quetiapine was initiated at 100 mg/day on the 7th day of his hospitalization and titrated to 300 mg/day by hospital day 10. With the addition of extended-release quetiapine, the patient’s depression, anxiety, insomnia, motivation and concentration improved. His suicidal ideation, auditory hallucination of hearing the video game, and somatic symptoms also resolved. The patient was discharged on the 11th day of his hospitalization, with a HAM-D score of 15 and a MADRS score of 18.

The patient was still attending his outpatient appointments with the community mental health clinic 2 months after discharge from the hospital, and was still taking full doses of lithium and extended-release quetiapine.

The Western Michigan University, Homer Stryker MD School of Medicine Institutional Review Board does not require ethics approval for reporting individual cases. The patient provided written informed consent for his information to be included in the present article and published in an international journal.

Discussion

A patient with bipolar depression with psychotic features presented early in the course of PMR. Given the severity of the PMR and bipolar history, we were concerned that his condition could evolve into catatonia, placing him at risk for dehydration, DVT and even a pulmonary embolism. Thus, we felt an urgency to treat this patient’s severe PMR with IM lorazepam. He was not on any psychotropic medications when administered IM lorazepam, and subsequent abrupt release of his severe PMR was observed. PMR did not return, probably due to maintenance of oral lorazepam, together with the initiation of lithium and quetiapine, which eventually stabilized his mood. His brisk response to IM lorazepam may have been possible because intervention began at the onset of PMR. The hypofunction of GABA-A receptors in the primary motor cortex during PMR may be compensated for by the increase in GABAergic tone following lorazepam administration.

The present patient’s response supports IM lorazepam as a treatment for severe PMR. We encourage other clinicians to consider using IM lorazepam at the onset of PMR to promptly reverse the symptoms and possibly halt progression to catatonia in patients with bipolar depression. We also recommend oral lorazepam maintenance and aggressive pharmacologic treatment of the mood disorder to prevent recurrence of PMR, as seen in other benzodiazepine studies.