Patient 1
A 53-year-old male began acting oddly about 1
month prior to being admitted to the hospital. His family reported that his speech was pressured, and that he had begun wandering about without seeming to know where he was going. He also had outbursts of anger and exhibited destructive behavior as well. After burning newspapers at home and threatening his family, he was sent to the emergency room and was then admitted to the psychiatric ward.
His medical history indicated that he had been diagnosed with bipolar I disorder at age 22 and had been hospitalized several times for treatment of manic episodes. He had been followed up at our clinic since he was 37
years of age. At age 49, he presented manic symptoms, including hyperactivity, incomprehensible speech, talking to himself, uncontrollable emotional outbursts, and destructive acts. After admission, he continued to have disorganized speech patterns, distractibility, and agitation. He exhibited grandiosity, had auditory and visual hallucinations, and showed occasional catatonia-like signs of excessive motor movement, purposeless walking around with mundane postures, and inexplicably squatting at corners. Because of his severe and worsening disorientation and marked inattention, a diagnosis of delirium and bipolar mania was entertained. Results of a detailed physical examination were unremarkable. No fever was detected and his blood pressure was normal. Vitamin B12 and folic acid levels were within normal ranges, and his electroencephalograms were normal. As a result, the diagnosis was changed to delirious mania. The physician proposed ECT, but the patient’s family refused it.
The patient was placed on a regimen of haloperidol decanoate, 50
mg/wk; valproate, 1500
mg/day (level: 53.89
mEq/L to 95.35
mEq/L); lithium carbonate, 600
mg/day (level: 0.35-0.74
mEq/L); trihexyphenidyl, 10
mg, and chlorprothexine, 100
mg/day. In addition, flunitrazepam, 2-4
mg/day, was given for severe insomnia throughout the patient’s hospitalization, with episodic augmentation of dormicum, 15
mg/day, and trazodone, 100
mg/day. Clonazepam, 4-10
mg/day, was prescribed for agitation. We considered decreasing the dosage of the antipsychotics, to avoid neurotoxicity, but this became impossible because the patient became ever more agitated and had to be restrained for longer periods.
About 15
days after he was admitted, we noticed he had general weakness, and replaced clonazepam with lorazepam, 1-7
mg/day, according to the severity of agitation. During this period, 2-4
mg of lorazepam was injected intramuscularly nine times for controlling his aggressive agitation from day 2 to day 33. After day 33, chlorpromazine, 25-50
mg, was injected intramuscularly three times for aggressive agitation because lorazepam had produced only a limited effect. Trihexyphenidyl, 10
mg/day, was used before admission and continued because of concern about the increased risk of the extrapyramidal syndrome (EPS). The patient had no obvious symptoms of EPS. Constipation was observed episodically, so 24
mg/day of sennoside was given initially and then replaced by dulcolax, 10
mg/day. On the 71
st day after admission, the patient was discharged without full remission. This occurred against his clinicians’ advice, but his family thought he had been hospitalized too long and they felt he seemed less agitated. His discharge medications remained the same, with the exception of the addition of oral haloperidol, 15
mg/day. His symptoms remitted about 2
weeks after discharge. His family claimed he took his medication as ordered after discharge.
At the latest admission, the patient’s manic behavior warranted close monitoring and frequent seclusion. His speech was rambling and pressured. His mood was elevated, and he was distracted, hostile. He impulsively and inappropriately touched other patients but not in a sexual manner and had urinary and fecal incontinence. He occasionally walked around aimlessly and once more squatted at corners purposelessly, which seemed to be catatonia-like signs. His delirium was worsening, with disorientation as to time and place. All this made his medical care very difficult.
The results of laboratory studies, including thyroid function tests, were normal. Physical examination showed no signs of inflammation or infection. The patient’s vital signs were normal. The clinical impression was delirious mania. The family once more refused ECT.
In an attempt to control his behavior, valproate (level: 66.44
mEq/L to 105.29
mEq/L), and lithium carbonate (level: 0.81
mEq/L to 1.16
mEq/L), were used concurrently with augmentation of his antipsychotic medication. The dose was titrated to maintain the valproate level at around 100
mEq/L and lithium at 1
mEq/L for expected maximal therapeutic effect. Trazodone, 100
mg/day, and lorazepam, 4
mg/day, were administered for their hypnotic effect. In addition, the antipsychotics were immediately started after the patient was readmitted. The initial agent selected was olanzapine (15
mg for 5
days), and this was then changed to quetiapine (50
mg for 3
days) and zotepine (100
mg to 200
mg for 1
month) in order to make him slightly sleepy. The manic symptoms gradually improved: Young Mania Rating Scale (YMRS) score declined from 42 (on day 9), peaked at 46 (day 16), then fell to 20 (day 30), and remained between 15-24. The patient’s YMRS score was 15 at discharge, but his delirium did not resolve. He seemed sleepy most of the time, but was episodically agitated and uncooperative with his treatment. His inattention and agitation made oral intake difficult and led to frequent choking. Nasopharyngeal tube feeding was sometimes needed. The hypoactivity with his sleepy state and slightly rigid limbs made catatonia and EPS difficult to rule out. But he had neither other catatonic symptoms such as echolalia nor hypertension and fever. Concern about EPS, catatonia, and anticholinergic-induced delirium led us to change the zotepine to quetiapine (400
mg to 500
mg for the remaining month) and to reduce the trihexyphenidyl dosage, from the initial 10
mg/day to 2
mg/day for the remainder of his hospitalization. At the same time, lorazepam was injected intramuscularly for agitation control, at a dosage of 1
mg/day (given one time) and 2
mg/day, given seven times from day 2 to day 77.
For financial reasons, the family arranged to have the patient transferred to another hospital. At discharge, he still had occasional delirium but he was much more cooperative with staff members. Two months later, he returned to our clinic, and was in near-remission but he had no clear memory about his treatment at the other hospital and thus couldn’t provide any information about the regimen at the other hospital.
Patient 2
A 58-year-old male had a history of bipolar I disorder and was being treated at a local clinic. His treatment regimen included lithium carbonate, 1500
mg/day, carbamazepine, 600
mg/day; haloperidol, 2
mg to 5
mg/day (titrated as needed); and trihexyphenidyl, 5
mg/day. His performance at work had deteriorated for several months prior to admission. Six weeks prior to admission, he began to show emotional lability, talking to himself, laughing hysterically, and exhibiting unusual behavior, such as remaining naked for an inappropriately long time after bathing. He presented at an outpatient clinic, displaying mania and was in a generally disorganized condition. Both delirium and dementia were suspected. His medication was adjusted at the clinic after symptoms developed, so this ruled out drug-induced delirium. After receiving 150
mg of zuclopenthixol, he showed general weakness and disorientation at night. Four days prior to admission, he had been treated with risperidone, 4
mg, and carbamazepine, 200
mg, because it was felt that the EPS might have been induced by use of traditional antipsychotics. He was finally admitted to the hospital because of irritability, loose associations, and talking to himself.
The bipolar disorder could be traced back to age 29, when his manic behavior led to hospitalization for 1
month. During that episode, disorientation was also noted. His wife denied any knowledge that he had abused substances in the past.
On admission, the patient presented with mixed symptoms of delirium and mania. He was inattentive, disorientated as to time, place, and person, and unable to find his bed. He was awake all night, busy without clear goals, spoke incoherently and had decreased appetite and intake. He took boxing stances and pumped his thigh at times without reason, showing catatonia-like symptoms. Electroencephalographic (EEG) results showed poor alpha waves and mild cortical dysfunction. The neurologist thought this was a normal pattern frequently seen in aging patients and indicated no specific illness. A computed tomography (CT) scan indicated an “aging brain,” with mild ventricular dilatation and mild widening of the cortical sulci. Vitamin B12 and folic acid levels were within normal ranges. Thyroid-stimulating hormone (TSH) levels were also within normal limits, while free thyroxine (T4) levels were slightly lower than normal (0.69
ng/dL; normal range: 0.7-1.48
ng/dL). Delirious mania was considered the cause for his delirium because there was no acute precipitating physical illness. His family refused the suggestion of ECT because they were not familiar with it.
After this, the patient was treated with risperidone, 4
mg/day, and valproate, 500
mg to 1000
mg/day (level: 98.28
μg/mL). On about the sixth day of treatment, he became oriented. The manic picture became much clearer in the following days. On the 11th day, lithium, 300
mg to 900
mg/day, was titrated up because the patient had gone several consecutive nights without sleep. On the 15
th day, quetiapine, 600
mg/day, replaced risperidone (4
mg/day) for his insomnia. When daytime drowsiness occurred for 2 consecutive days, quetiapine was then replaced by olanzapine, 20
mg/day. For insomnia, estazolam, 4
mg, or flunitrazepam, 2
mg, was used, depending on the severity of the insomnia. But lorazepam, 2
mg/day, was given 3 times, and zolpidem, 10
mg/day, or zopiclone, 15
mg/day, was administered 17 times more episodically as the patient’s insomnia worsened. The patient was discharged in partial remission about 1
month later because the family chose to care for him at home. The regimen at discharge was olanzapine, 20
mg/day; flunitrazepam, 2
mg/day; trihexyphenidyl, 6
mg/day (successfully treating the drug-induced EPS and rigidity of limbs); magnesium oxide, 750
mg/day; and lithium, 900
mg/day. The patient’s mood stabilized over the next 2
months, and there was no recurrence of delirium.
Patient 3
A 67-year-old male began an active campaign for local elective office 1
month before being admitted to the hospital’s psychiatric unit. After 2
weeks of campaigning, he developed pressured speech and irritability, remained outside all day, and increased his normal intake of food and fluids. A week later he had insomnia, confusion, an unsteady gait, and frequent falls. On the day of admission, he was found kneeling in the street.
The patient had a history of peptic ulcer, pyloric stenosis, gallstones, and adhesive ileus that had been treated by vagotomy, gastrectomy, cholecystectomy, and enterolysis. His first episode of depression occurred at age 58. He was admitted twice for manic episodes, and the last psychiatric hospitalization was 5
years prior to this admission. His regular regimen included lithium carbonate, 600
mg/day; trihexyphenidyl, 2
mg/day; clonazepam, 3
mg/day; and diazepam, 4
mg/day. A month before admission, bupropion, 75
mg/day, and olanzapine, 10
mg/day, had been added to help stabilize his mood.
After admission, he had the typical picture of mania, with euphoria, pressured speech, and over-involvement with other individuals, and he created frequent interpersonal conflicts on the ward. Bupropion was discontinued immediately. Because of tongue dyskinesia, the olanzapine was changed to quetiapine, 400
mg/day. Three weeks later, delirium appeared. He became disoriented. He was frightened by visual hallucinations, and angry at the staff, whom he believed had transported him to “the train station.” His lithium level was 0.41
mEq/L to 1.18
mEq/L while he was hospitalized. His white blood cell count (WBC) was elevated to 18100/uL, Segment 83%, but there was no fever or evidence of infection. He had an inguinal hernia, which was believed to be the source of his leukocytosis, but the hernia could be moved in place by the surgeon without any sign of infection. Two weeks later, the WBC count decreased to 6900/uL without antibiotics. Thus, infection was ruled out as a possible cause for delirium. The results of electrolytes and renal and hepatic function tests were normal. Results of CT scans were unremarkable. On the 12
th day, an abnormal EEG was recorded, with mild-to-moderate cortical dysfunction without epileptic findings. The patient’s delirium persisted, along with persecutory delusions, fear of eating, and with agitation, kicking, and shouting. Delirious mania was suspected.
Bilateral ECT was begun on the 29
th hospital day, and performed 3 times a week. After the fourth session, the patient’s orientation improved, but there were also signs of depression. Before the patient presented with depressed mood, he accepted 2-mg injections of lorazepam for agitation. The injections were given 14 times from day 4 to day 34, and 2 doses were given before delirium occurred. After the fifth session of ECT, his depression worsened. He tried to leap from his bed in a suicide attempt after the sixth session of ECT. He was totally oriented after the seventh session, but his depression persisted. Paroxetine, 10
mg/day, was started after the 12
th ECT session, and lithium, 600
mg/day, was resumed after the 16
th session. The patient’s depression improved after 17 sessions of ECT, and resolved completely a month later. The discharge regimen included: alprazolam, 1.5
mg/day; paroxetine, 10
mg/day; lithium, 600
mg; zopiclone, 15
mg/day; and loperamide, 2
mg/day. Loperamide was added to the regimen because the patient had diarrhea when he ate watery foods without his dentures.
Patient 4
A 50-year-old female had a 15-year history of bipolar disorder, which had resulted in four previous hospitalizations for manic episodes. She was admitted to the nearby mental health institute after 1
week of recurrent mania. During that hospitalization, clinicians noted a change in her level of consciousness. She developed aspiration pneumonia with respiratory failure, and an endotracheal tube was inserted. The patient was uncooperative and removed the endotracheal tube. She was transferred to our medical department and seen in consultation by a psychiatrist.
Because of obvious manic symptoms of euphoria with auditory hallucinations, incoherent speech, disorganized behavior, and impulsively touching others’ faces, she was transferred to the psychiatric ward after 5
days of medical stabilization.
Her medication was changed from aripiprazole, 10
mg to 15
mg/day (titrated up to control manic symptoms), to quetiapine, 600
mg/day (replacing aripiprazole for insomnia); clonazepam, 3
mg/day; lithium, 600
mg/day (level: 0.2 to 0.47
mg); and lorazepam, 4
mg at bedtime. In addition, lorazepam, 2
mg/day, was intramuscularly injected on days 7 and 9 to control agitation. After this, the patient was calm for hours. In addition to her manic symptoms, she had prominent catatonic symptoms. She alternated between excitement and mutism. She also displayed episodic absent-mindedness, with a staring expression, echolalia, and echopraxia. Because of her refusal to eat or drink and frequent aggressiveness, she required nearly constant restraint of her hands and had to be fed via nasogastric tube. These catatonic symptoms progressed while delirious symptoms appeared as disorientation to time and place with chaotic consciousness 3
weeks after the onset of mania. Fever subsided before delirium appeared and the WBC count decreased from 13600 to 7100. A diagnosis of catatonia and delirious mania was made, and bilateral ECT was begun on the 10
th day of delirium. The delirium subsided after the first session of ECT and totally resolved after the second session, although mania and psychosis remitted after the sixth session.
Patient 5
A 59-year-old male was admitted to the hospital with elevated mood, irritability, irrelevant speech, hyperactivity, poor sleep, odd feelings he described as an “earthquake,” and auditory hallucinations.
He had a history of bipolar I disorder beginning at age 32. He borrowed money irrationally with unclear plans for its use, wandered around outside; slept poorly; and ate sugar canes at another person’s fruit farm without permission. His unusual symptoms occurred episodically, usually lasted about 10
days, and resulted in several hospitalizations. At age 52, he underwent a frontoparietal craniostomy because of an intracranial hemorrhage after a traffic accident. Severe recent memory impairment was observed after that accident. At age 54, he had a single transient ischemic attack with left upper limb weakness, but totally recovered. During outpatient psychiatric follow-up, he once overdosed in an apparent suicide attempt during a depressive episode. Because of weight gain and depression, his dosage of risperidone, 3
mg/day, was discontinued 10
months prior to admission. Aripiprazole, 20
mg/day, and paroxetine, 10
mg/day, were added to his treatment regimen, along with extended-release valproate, in a dosage of 500
~
750
mg/day, according to clinical response. However, drug compliance was poor throughout the course of bipolar disease in his life. The paroxetine was discontinued at a clinic visit 15
days before the patient was admitted after he had experienced 2
days of insomnia, irritability and grandiose thoughts.
When he was first admitted, aripiprazole, 20
mg/day, was changed to immediate-release quetiapine, 400
mg/day, to control insomnia while he was hospitalized. In addition, lorazepam, 4
mg, was administered for insomnia. Three days after admission, delirium occurred. He became disoriented about time and place. Inattention and irrelevant speech were apparent, but his orientation occasionally improved. A CT scan showed right temporoparietal region postcraniotomy and generalized brain volume loss with dilatation of sylvian fissures, cerebral sulci, and ventricles, consistent with damage following a past cerebrovascular accident (CVA). Results from biochemistry and hematologic examination were unremarkable. The patient’s symptoms improved without full remission. Against medical advice, his family insisted that he be discharged on the 10th hospital day. A week later, he was fully oriented but it took an additional month for his mood to return to baseline levels.
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