Coadministration of parenteral olanzapine and a benzodiazepine can lead to severe orthostatic hypotension and cardiac or respiratory depression and should be avoided in geriatric patients.14 Finally, it is important to rule out presentations that may worsen with antipsychotic treatment, including phencyclidine (PCP) toxicity (could worsen dystonic reactions), anticholinergic delirium, neuroleptic malignant syndrome (NMS), or catatonia.
If a patient does not respond to the initial dose of a medication, the dose may be repeated. However, doses should not be repeated until a patient is so sedated that he or she cannot take part in his or her care, or until he or she has developed significant EPS.
In addition to antipsychotics, consider loading with oral divalproex for patients who are acutely psychotic in the context of a manic episode (Table).15,16 Higher serum divalproex levels—target serum levels >94 μg/mL—are associated with greater efficacy as measured by change from baseline in Mania Rating Scale or Young Mania Rating Scale scores compared with placebo.15 For acutely psychotic schizophrenia patients, there is evidence of benefit with initial treatment with divalproex combined with an SGA. In a randomized, double-blind study, patients treated with divalproex plus olanzapine or risperidone showed quicker initial resolution of psychotic symptoms compared with olanzapine or risperidone monotherapy, but no better long-term benefit.16 Clinicians may consider this well-tolerated combination after an appropriate medical workup. This finding of early benefit was not replicated with divalproex extended-release.17
Table
Divalproex dosing for patients with acute psychosis and mania
| Initial dose | Titration | |
|---|---|---|
| Acute mania15 | Divalproex delayed-release: 750 mg/d Divalproex extended-release: 20 mg/kg/d | Increase to clinical effectiveness or maximum serum level of 125 μg/mL |
| Exacerbation of psychosis16 | Divalproex: 15 mg/kg/d (in 2 doses) | Increase to clinical effectiveness over 12 days or maximum dosage of 30 mg/kg/d |
Side effects and adverse reactions. Treatment with antipsychotics may cause QTc interval prolongation, which can lead to increased risk for torsades de pointes and sudden death due to ventricular fibrillation. However, there have been few cases of torsades de pointes after oral haloperidol and none with IM haloperidol compared with at least 30 cases of torsades de pointes after IV haloperidol treatment. Torsades de pointes after risperidone, olanzapine, or ziprasidone treatment has not been reported.18
Hypotension and bradycardia may occur in patients treated with olanzapine; however, these signs occur less frequently in agitated patients.18 Antipsychotic treatment increases risk for EPS, including acute dystonia, akathisia (subjective restlessness with desire to move), and parkinsonism (shuffling gait, resting tremor, rigidity and bradykinesia), as well as NMS.
Nonpharmacologic interventions. Verbal intervention to try to de-escalate an agitated, psychotic patient should be attempted first; however, this is not always possible. Other behavioral interventions include offering a meal, blanket, or pillow, or other comforting options to decrease the patient’s anxiety associated with psychosis.2 However, if agitated psychotic patients continue to display aggressive behaviors and pose a risk of harm to themselves or those around them, physical restraints should be considered because the clinician must balance protecting the patient’s rights with others’ safety. If physical restraints are used, medication also should be administered. Remove physical restraints as soon as safely possible; the Joint Commission has established standards for minimizing harm when using physical restraints.19
Diagnostic workup
Once a patient is medically stable in the ER, begin further workup of the etiology of the psychosis (Algorithm 2). All patients should have a physical exam, provided they are calm and in behavioral control. Monitor vital signs; patients at risk of withdrawal from substances should be monitored more frequently. Although there is no established standard for “medical clearance” of a psychiatric patient,20 all patients should undergo basic laboratory tests, including basic metabolic panel, complete blood count, and urine toxicology. The extent of the workup is determined by the clinical situation and suspected cause of psychosis.21
Algorithm 2: Diagnostic workup of an acutely psychotic patient
ER: emergency room; EEG: electroencephalography; LP: lumbar puncture; TSH: thyroid-stimulating hormone
If you suspect delirium, the underlying medical etiology must be identified and treated. Up to 40% of hospitalized patients with delirium may have psychosis.22 Psychosis in a delirious patient may be characterized by poorly formed delusions and visual hallucinations. Delirious patients often are inattentive, easily distracted, and disoriented, with a fluctuating clinical course. Patients with psychosis generally do not have impaired attention and are alert with intact memory. However, acutely psychotic patients may be quite disorganized and uncooperative, which makes it difficult to distinguish between these 2 diagnoses. Serial exams may help clarify the clinical picture. It is important to remember that patients with a history of a psychotic disorder may have a superimposed delirium.