Description

The patient is a 44-year-old, African-American woman who was admitted to a forensic psychiatric hospital as incompetent to stand trial for alleged arson of an inhabited structure, battery, and exhibiting a deadly weapon. Upon admission, she was found to be argumentative and paranoid. Her risk for violence was elevated due to her irritability, sensitivity to provocation, and being easily angered when requests were denied. She also experienced auditory hallucinations of her name being whispered and visual hallucinations of snakes. She was an unreliable historian, and no records were available for review. Admission laboratory analyses were unremarkable, except for being hepatitis C positive. Her urine admission drug screen was negative, and she refused to have an electrocardiogram.

Despite several weeks of adherence to olanzapine 20 mg (increased to 40 mg) and mirtazapine 30 mg, she remained irritable, paranoid, and violent. She engaged in repeated verbal threats and occasional episodes of physical aggression, resulting in five-point restraints on one occasion, wrist-to-waist restraints on two occasions, and a period of one-to-one nursing observation. Mirtazapine was discontinued as it was deemed unnecessary and was possibly promoting irritability via enhancing norepinephrine release. It was difficult to determine whether the removal of mirtazapine had an appreciable effect on her irritability, since she had an increase in olanzapine to 50 mg at the same time. After steady state was established on a daily dose of 50 mg, her AM trough olanzapine plasma concentration was measured at 78 ng/ml. Olanzapine was then increased to 60 mg to achieve an increased olanzapine plasma concentration with an ultimate target plasma concentration greater than 100 ng/ml, if clinical response at lower concentrations was inadequate. After 11 days, she was no longer paranoid and reported that her auditory and visual hallucinations were gone; however no olanzapine level was obtained at the 60 mg dose. Clonazepam 1.5 mg and quetiapine 50 mg were added after several days on the increased olanzapine dose to assist with residual irritability and initial insomnia, respectively. Her cognitive ability to learn court-related material improved, although she would occasionally become loud and intrusive. Divalproex sodium, extended release, was initiated with the dose titrated to target her irritable and intrusive episodes. An AM trough valproic acid serum concentration of 72 mcg/ml was achieved while on a daily dose of 1500 mg, and she became calmer within 17 days of starting the medication. She was discharged and returned to court 3 months after admission. The prescribed medication regimen at discharge included olanzapine 50 mg daily, divalproex 1500 mg daily, clonazepam 1.5 mg daily, and quetiapine 50 mg each evening.

Commentary

A high dose of olanzapine helped to control this patient’s psychosis and reduced the majority of her violence. The addition of divalproex was effective in alleviating her residual irritability and intrusiveness. Since some patients have shown tolerability and efficacy with higher-than-typical antipsychotic blood levels, correlating with D₂ receptor occupancy in the upper ranges of tolerability (80% and greater), it is possible that reaching the targeted olanzapine plasma concentration of 100 ng/ml would have avoided the need for additional medication [7]. In addition, the use of valproic acid or divalproex should target a plasma concentration of 80–120 mcg/ml to allow sufficient non-protein-bound valproic acid to have its optimal CNS effect [8].

An alternative explanation to the patient’s responsiveness to divalproex and benefit from stopping mirtazapine, is that the patient suffered from a bipolar spectrum disorder. If a therapeutic trial of medication directed at signs and symptoms of a diagnosis lacks efficacy, revisiting the diagnostic formulation should be considered, in addition to efforts to augment the initial medication trial. Nevertheless, the patient’s presentation and antipsychotic response to high-dose olanzapine appeared most consistent with her psychotic violence being driven by a schizophrenia spectrum disorder.

Description

The patient is a 48-year-old, Hispanic male with a longstanding history of schizophrenia who was admitted to a forensic psychiatric hospital as not guilty by reason of insanity for assaulting his board and care roommate due to his delusions. Prior to hospital admission, he had been taking fluphenazine decanoate 50 mg intramuscularly (IM) every 2 weeks, fluoxetine 20 mg daily, quetiapine 200 mg twice daily, and benztropine 1 mg twice daily. He had previously had trials of olanzapine, ziprasidone, quetiapine, divalproex, and lithium. His medical conditions included hepatitis C and an extensive history of substance abuse, including alcohol, cannabis, cocaine, inhalants, opiates, and methamphetamine.

Upon admission, he was unkempt, paranoid, and reported having command auditory hallucinations. Laboratory analysis was done at admission, and the following abnormalities were noted: platelets 103 × 10³/ul (low); uric acid 7.5 mg/dl (high); ALT 49 u/l (high); AST 52 u/l (high); amylase 320 u/l (high); and hepatitis C RNA quantitative PCR 6.2 log IU (high). His lipase level was within normal limits, and amylase isoenzyme analysis revealed normal pancreatic amylase isoenzymes with elevated salivary isoenzymes. He was prescribed quetiapine 500 mg daily, fluphenazine decanoate 50 mg IM every 2 weeks, lithium carbonate 600 mg each evening, and temazepam 30 mg each evening. Quetiapine was increased to 800 mg daily after 14 days due to frequent episodes of psychomotor agitation in response to psychotic stimuli. Later, olanzapine 20 mg was added due to ongoing psychosis and agitation. His liver transaminase enzymes normalized, as did his amylase, within 30 days of admission. Despite continued low platelets, a trial of divalproex sodium (extended release) was initiated to augment the antipsychotic medication; however, tremor and transaminase elevations led to its discontinuation after one week. Lithium was stopped due to tremor, as well.

His episodic agitation and violence due to unremitting psychosis remained problematic. The daily dose of olanzapine was increased to 60 mg, 47 days after admission, and quetiapine was decreased to 200 mg daily. He remained intrusive (would stand over patients’ beds at night and stand close to them during the day), would frequently curse loudly to himself and at staff without provocation, and would occasionally strike peers and staff. He had steady state plasma concentrations of fluphenazine 0.6 ng/ml and olanzapine >200 ng/ml with extrapyramidal side effects in the form of parkinsonism without akathisia or dystonia.

Owing to his treatment-resistant psychosis, his treating psychiatrist initiated a clozapine trial, as olanzapine and quetiapine were tapered and discontinued. Clozapine was titrated to a dose of 300 mg daily, resulting in a trough clozapine plasma concentration of 799 ng/m with mild sialorrhea. The patient’s psychosis persisted. However, his cursing decreased, and he was no longer threatening and hitting others. After 8 weeks on the same dose of clozapine, his auditory hallucinations and visual hallucinations were substantially decreased. His clozapine plasma concentrations ranged from 688–850 ng/ml on the same dose, and the medication was well tolerated with episodes of violence remaining absent for over a year to date.

Commentary

This patient had a notably low fluphenazine plasma concentration (0.6 ng/ml) when measured at the hospital. When fluoxetine was discontinued upon admission, the fluphenazine metabolism was no longer inhibited via fluoxetine’s influence on CYP2D6, leading to a decline in the fluphenazine plasma concentration of roughly 50%. Checking for this pharmacokinetic drug–drug interaction and measuring a baseline fluphenazine plasma concentration upon admission would have allowed maintenance of fluphenazine plasma concentrations within the therapeutic range. Nevertheless, this patient’s psychosis persisted during antipsychotic trials both in the hospital and prior facility, leading to a clozapine trial. Clozapine has a superior response rate compared to other antipsychotics for treatment-resistant schizophrenia and shows efficacy in decreasing aggressive behavior independent of its antipsychotic properties [9–11].

Description

The patient is a 51-year-old, African-American male who was admitted to a psychiatric forensic hospital after he was found not guilty by reason of insanity for attempted rape. After admission to the hospital, he was continued on oral haloperidol 10 mg twice daily and valproic acid 2000 mg each evening. Admission laboratory tests revealed normal chemistries and a negative urine drug screen. The electrocardiogram on admission showed nonspecific T wave abnormalities with a ventricular rate of 79 bpm and QT/QTc of 389/396 msec.

The patient had a history of ADHD with impulsiveness and aggression beginning in adolescence. His level of aggression in his youth led to criminal charges and institutionalization beginning at 14 years of age. Later in adolescence, he developed a psychotic illness with persecutory delusions that progressed into a schizophrenia-spectrum disorder. His clinical picture was complicated by the presence of borderline intellectual functioning. Previous medication trials included chlorpromazine, fluphenazine, loxapine, risperidone, paliperidone, paliperidone palmitate, olanzapine, quetiapine, thiothixene, fluoxetine, paroxetine, mirtazapine, lithium carbonate, valproic acid, lamotrigine, gabapentin, tiagabine, clonidine, and buspirone.

His history of treatment with a variety of antipsychotics and mood stabilizers in both monotherapy and polypharmacy resulted in a partial response at best, with his psychosis showing only a modest improvement in response to medication. However, his aggression and impulsivity persisted. Medications used in the course of his current hospitalization included olanzapine, fluphenazine decanoate, and lithium carbonate. Consistent with his prior history, his psychosis improved, but the agitation and impulsive aggression continued.

Once his psychosis was under moderate control, he was assigned a nursing staff member (Behavioral Change Agent, BCA) who would spend one shift daily working with the patient to assist him with the use of coping strategies other than aggression. The BCA would interface with other team members to provide greater consistency in the behavioral approach to the patient. The assigned nursing staff member (BCA) assisted the patient and his team in recognizing his triggers to violence that led to a modest reduction in threats, though his PRN medication use increased. Despite the use of the BCA, the patient continued to engage in violence against his treatment team. The addition of methylphenidate extended release (Concerta ER) appeared to improve his concentration and attention, and his BCA observed that the patient had an improved ability to implement use of his coping strategies. At that point, his medication regimen included olanzapine 50 mg each evening, divalproex (extended release) 2500 mg each evening (switched from lithium due to lithium-related tremors), fluphenazine decanoate 75 mg every 14 days, and methylphenidate extended release 54 mg daily.

He was enrolled in a multifaceted neurocognitive and social cognition training program for patients with psychiatric disorders and severe cognitive needs and challenges. The program was specifically designed to target aggression to self and others. His medication regimen remained stable, and he continued to have the services of the BCA while also attending the new aggression-reduction program. His use of PRN medications decreased from 78 in the 21 months prior to starting the program to a total of 8 in the 36 months while enrolled. His episodes of seclusion/restraint dropped to zero from a baseline of two occurrences per year. His aggressive acts showed a reduction from his average of 4.5 serious episodes per year to only one incident in the current year.

Commentary

Violence that persists after controlling the psychosis is predatory or impulsive. Since this patient’s violence was impulsive, enhancing attention with a stimulant seemed to, indeed, improve attention, but this addition was not sufficient alone. Structured psychosocial and cognitive skills programs were required to obtain the most substantial reductions in violence [12–14].

Description

The patient is a 45-year-old, African-American male who was admitted to a forensic psychiatric hospital when he was 23-years-old after being found not guilty by reason of insanity for entering a home he believed he owned and threatening the homeowner with a knife.

Upon admission, the patient was disheveled, guarded, and reported persecutory delusions, ideas of reference, and thought broadcasting. He had several healed fractures from prior fights but no other medical conditions. Admission laboratory tests were unremarkable, showing values within normal limits.

His history of mental illness began at 16-years-old with his experience of auditory hallucinations. Characteristic signs and symptoms of his illness consisted of auditory hallucinations, persecutory delusions, grandiose delusions, disorganized thinking, disorganized behavior, social isolation, assaults, and sexually inappropriate behaviors. His course of illness had been complicated by substance abuse, including early adolescent use of alcohol, cannabis, and inhalants. Later in adolescence, he began abusing methamphetamine, psilocybin, and cocaine.

His psychosis improved early in the course of hospitalization. He was treated with haloperidol 10 mg twice daily (later, converted to haloperidol decanoate 200 mg IM every 28 days due to his refusal to take oral haloperidol), valproic acid 1500 mg twice daily (targeting his affective fluctuations, often in response to internal stimuli), clonazepam 1 mg twice daily (targeting his irritability), and trazodone 400 mg each evening (for insomnia). His auditory hallucinations disappeared, and he had significant improvement in the level of organization of his speech and behavior. He continued to experience some persecutory delusions with occasional ideas of reference that other people were talking about him when he passed them.

Despite the improvement in his psychosis, he made frequent threats toward staff and peers when his desires were not met. He was involved in several physical altercations with peers and assaulted a staff member early in his hospitalization. He also engaged in rules violations, such as gambling, smoking on the unit, collecting contraband items, and making sexually inappropriate remarks and gestures, such as masturbating in front of staff, touching female staff on the breasts and buttocks, and soliciting sexual favors from them. His level of violence increased during his hospitalization, such that he assaulted a peer with an object, striking him repeatedly in the head and face. Ten days later, he went on to attack several staff members, injuring two of them severely. He was convicted of assault and sent to serve a term in prison.

Upon his return to the forensic inpatient setting, he resumed many of the same behaviors, including rules violations, threats, and assaults. His psychotic symptoms remained well controlled; however, his disruptive behaviors and violence increased after the psychosis improved. The frequency and severity of his violence increased to the point that he required unit transfers approximately every 3 months. Several attempts were made to guide him toward more pro-social conduct, including skills building, anger management group participation, and the development of individualized behavior plans on various units. He was referred to the behavior specialist team that assisted in the development and implementation of his behavior plans. He showed an initial decrease in physically aggressive episodes per month (from eight to five, at one point). However, such improvements were short-lived.

Due to his persistent violence in the hospital setting, he was assessed by a forensic examiner for referral to a prison setting. The examiner noted that the patient had 33 incidents of threats, sexually inappropriate behavior, and violence over the 1 month period prior to his forensic evaluation. As a result, he was transferred to a prison setting, where he has been less violent and disruptive according to prison records.