A 34-year-old Caucasian male was admitted to the Department for Psychotic Disorders at the Institute of Mental Health in Belgrade, Serbia, presenting with a depressive episode associated with schizoaffective disorder.
His first psychiatric symptoms emerged at the age of 14, manifesting as obsessive thoughts, compulsions, and aggressive behavior towards family, peers, and school property. Initial psychiatric treatment at the Clinic for Child and Adolescent Psychiatry led to a diagnosis of schizoaffective disorder, with subsequent initiation of lithium and clozapine therapy. Throughout adolescence, the patient experienced three psychiatric hospitalizations at the aforementioned clinic due to self-initiated discontinuation of prescribed medication resulting in recurrent decompensations. The fourth hospitalization, at age of 22 (the first in adulthood), followed aggressive behavior towards family members and lead to the introduction of olanzapine 5mg, valproate 500mg, and diazepam 30mg into his treatment. Despite a stable period over the next five years, a gradual tapering of psychopharmacotherapy led to a decline characterized by recurrent aggressive outbursts, resulting in three additional hospitalizations at the local psychiatry department in the place of residence between ages of 28 and 33.
The patient’s psychiatric treatment at the Institute of Mental Health in Belgrade began in May 2024, at the age of 34 years. Upon admission, a significant portion of the psychiatric medical records pertaining to previous treatments were unavailable due to patient’s destruction of these documents during a prior exacerbation. Consequently, the available information about past psychiatric treatments and prescribed psychotropic medications was derived from the remaining medical records. According to collateral information, the last prescribed therapy before admission to IMH consisted of levomepromazine 100mg and valproate 1500mg daily.
Upon admission, the patient reported experiencing marked apathy, low energy, and significantly diminished motivation over the past six months. He struggled with daily tasks, neglecting his agricultural responsibilities and familial duties. Additionally, he reported tearfulness and persistent insomnia. He denied any history of head injuries, loss of consciousness, or serious somatic illnesses, although he acknowledged occasional alcohol consumption over the past fifteen years, sometimes to the point of intoxication. The information provided about the amount and frequency of alcohol consumption should be interpreted with caution, due to the patient's tendency to minimize their intake. There was no history of use of other substances. Family history revealed a familial burden of psychiatric illnesses, including a brother with intellectual disabilities requiring special education, and a paternal grandfather who died by suicide.
On initial assessment, the patient appeared well-groomed, slightly older than his stated age. He was cooperative but demonstrated slight psychomotor retardation with decreased spontaneous movements and reduced facial expressions. He established and maintained eye contact and verbal communication, answered questions in a direct and logical fashion, although with prolonged reaction time. His speech was slow, with a monotonous tone and reduced spontaneity. His mood was moderately to severely depressed, his affect was congruent with thought content, with no visible intensive fluctuations. Anxiety was evident through restlessness and fine hand tremor. Thought processes were logical and coherent but slowed. The content of thought was dominated by Beck's cognitive triad, with nihilistic ideation but denied suicidal or self-harm thoughts. There were no delusions, hallucinations, or obsessive-compulsive symptoms. The patient was alert and well oriented to self, person, place and time. Concentration was impaired as evidenced by difficulties with simple calculations. Immediate and recent memory was mildly impaired. Intelligence was estimated to be in the low-average range with difficulties in abstract thinking. Insight into the illness was fair, with recognition of the need for treatment. Judgment was intact regarding personal care but impaired in terms of complex decision-making. On physical examination, the patient appeared well-nourished and hydrated. Vital signs were within normal limits. A congenital right eyelid ptosis was noted. No evidence of neurological deficits was found.
Blood analyses upon admission revealed minor, clinically insignificant variances in creatinine levels (58 µmol/L, reference range: 62 to 106 µmol/L), uric acid (524 µmol/L, reference range: 143 to 416 µmol/L), and sedimentation rate (14 mm/h, reference range: 2 to 12 mm/h), while all other parameters fell within normal limits. Upon admission, therapy adjustment commenced, involving a gradual reduction in the daily dosage of valproate and the introduction of lithium. Persistent insomnia prompted the medical team to administer additional peroral therapy for several consecutive nights, consisting of 15 mg of midazolam, followed by 10 mg of zolpidem, 50 mg of quetiapine, and 10 mg of diazepam. Nevertheless, the patient experienced less than two hours of continuous sleep.
Following the intramuscular administration of 50 mg of chlorpromazine in the evening therapy for persistent and refractory insomnia fourth day upon admission, the patient exhibited agitation, failed to establish verbal communication despite being awake, displayed disorganized behavior, and presented with pale, diaphoretic skin in the morning. Vital signs recorded included a body temperature of 37.7°C, blood pressure of 150/90 mmHg, and blood glucose level of 8.4 mmol/L. Rigidity and hypertonicity were observed in the arm and neck muscle groups bilaterally. During the physical examination, the previously non-verbal patient suddenly began conversing fluently in English (which he had learned during childhood but had never spoken outside of school), primarily inquiring about the hospital’s location and the reason for his presence. This episode lasted approximately 5 minutes, after which the patient reverted to non-communication with the medical staff.
Due to suspicion of developing NMS, all previous psychopharmacotherapy was discontinued. The following treatments were administered: 500 ml of 0.9% NaCl solution with vitamin B and C intravenously, 5 mg of biperiden hydrochloride intramuscularly, and 2.5 mg of lorazepam orally three times a day. A blood sample was sent for urgent laboratory analysis, which confirmed the suspicion of NMS showing elevated creatine phosphokinase (CPK) values at 1662 IU/L (reference range: 20 to 200 IU/L) and leukocytosis at 9.5x10^9/L (reference range: 4.0 to 9.0 x10^9/L). Additionally, there were several other clinically less significant deviations: sodium 133.0 mmol/L (reference range: 136.0 to 145.0 mmol/L), chlorides 96.0 mmol/L (reference range: 98.0 to 107.0 mmol/L), uric acid 435 µmol/L (reference range: 143 to 416 µmol/L), AST 84 IU/L (reference range: <40 IU/L), CRP 10.52 mg/L (reference range: <5 mg/L), and direct bilirubin 5.7 µmol/L (reference range: <5 µmol/L).
Several hours after the administration of the parenteral therapy the patient felt better. On the same day, he was thoroughly examined by an internist. Subjectively, he complained of difficulty speaking, slowness, and instability while walking. Objectively, he was eupneic, obese, subfebrile (body temperature 37.5°C), and his extremities were without swelling. Lung auscultation revealed normal breath sounds, and heart auscultation revealed clear tones without murmurs. His blood pressure was 125/80 mmHg. An ECG showed sinus rhythm with a heart rate of 100 beats per minute, and the ST and T waves were unremarkable. The therapy was adjusted to include bisoprolol 2.5 mg in the morning and amoxicillin/clavulanic acid (875 mg/125 mg) twice daily, along with the parenteral administration of one liter of infusion solution daily (0.9% NaCl with vitamins C and B). After two days, repeat blood biochemical analyses showed a slight decrease in CPK levels (1416 IU/L). For a detailed comparative presentation of the blood laboratory analysis results, see Table 2.
Table 2
Comparative presentation of blood analysis results
| Laboratory analysis (reference range) | Upon admission – day 0 | Suspicion of NMS – day 5 | Follow-up - day 7 | Follow-up - day 11 | Follow-up - day 12 |
| Sodium (136.0-145.0 mmol/l) | 144.0 | 133.0 | 138.0 | 136.0 | 140.0 |
| Chlorides (98.0-107.0 mmol/L) | 104.7 | 96.0 | 102.1 | 101.9 | 104.1 |
| Creatinine (62–106 umol/l) | 58 | 70 | 57 | 53 | 56 |
| Urea (1.7–8.3 mmol/l) | 2.8 | 4.0 | 3.5 | 3.5 | 3.9 |
| Uric acid (143–416 µmol/L) | 524 | 435 | 468 | 403 | 373 |
| AST (< 40 IU/L) | 19 | 84 | 111 | 39 | 32 |
| ALT (< 41 IU/L) | 15 | 36 | 50 | 46 | 41 |
| Direct bilirubin (< 5 µmol/L | / | 5.7 | / | 2.3 | 1.4 |
| Albumins (30–50 g/L) | / | 51 | / | 48 | 48 |
| CPK (20–200 IU/L) | / | 1662 | 1416 | 344 | 212 |
| Total leukocyte count (4.0–9.0 x10^9/L) | 5.9 | 9.5 | / | 7.4 | 7.8 |
| Platelets (150–350 x10^9/L) | 243 | 295 | / | 360 | 358 |
| CRP (< 5 mg/L) | / | 10.52 | / | 1.47 | 1.14 |
| Sedimentation (2–12 mm/h) | 14 | 4 | / | / | 4 |
| Note: Only the laboratory analysis results that deviated from the reference values at any point during the monitoring are shown; “/” – the analysis was not performed at the given time point. |
- Insert Table 2 here -
Over the following days, two additional internal medicine check-ups were conducted with repeated blood laboratory analyses (refer to Table 2 for details). Parenteral and oral rehydration therapy continued, accompanied by ongoing monitoring of vital signs. The patient remained afebrile, with pulse and blood pressure consistently within normal ranges. Consequently, antibiotics were discontinued after one week, along with bisoprolol. The patient was also examined by a neurologist and an EEG recording was performed. Besides the congenital anomaly of the left eyeball the neurological exam was unremarkable. EEG showed low amplitude basic activity and drug-induced acceleration, without pathological changes. A brain MRI was indicated to be performed after discharge from hospital treatment. Upon stabilization, a psychological assessment was also conducted, indicating low-average intellectual functioning (total IQ 79, verbal IQ 78, performance IQ 77). The personality inventory showed self-defeating and depressive personality dimensions, high level of internal anxiety, and persistent vulnerability to disorganization in response to daily life stressors.
Concurrently, the patient's mental state gradually improved, with persistent insomnia and evening irritability as the sole remaining symptoms. Following stabilization of the laboratory parameters, quetiapine was gradually initiated in the evening (dose gradually increased to 200 mg), followed by reduction in the daily lorazepam dose. This resulted in normalized sleep patterns and initial remission upon discharge.