Antipsychotic Use Guidelines

Patient Characteristics and Medication Use

• The use of high-potency antipsychotics, high doses, advanced age, female sex, and prior brain damage are associated with increased risk of adverse effects, and concomitant use of lithium is also a consideration, as recommended by the British Journal of Psychiatry 1
• The British Journal of Psychiatry recommends using low doses of antipsychotics, especially in first-episode psychotic patients, and preferring atypical antipsychotics over typical ones 1

Medication Dosing and Monitoring

• Initial doses of antipsychotics, such as risperidone 2 mg/day or olanzapina 7.5-10.0 mg/day, should be used with frequent monitoring of extrapyramidal effects, as recommended by the British Journal of Psychiatry 1
• For acute anxiety/agitation, lorazepam 0.25-0.5mg for children and 0.5-1mg for adolescents/adults may be used, with short-term use of benzodiazepines, as recommended by the American Academy of Pediatrics 2
• Midazolam 2.5mg SC/IV PRN (up to 5mg maximum) may be used for acute anxiety/agitation, as recommended by the Annals of Oncology 3
• SSRIs or SNRIs are first-line treatments for longer-term management of persistent anxiety, with demonstrated efficacy and NNT = 4.70 for SSRIs and NNT = 4.94 for SNRIs, as suggested by the American Academy of Child and Adolescent Psychiatry 4
• When using antipsychotics, monitor for extrapyramidal symptoms (EPS) including akathisia, which can mimic anxiety, as recommended by the Journal of the American Academy of Child and Adolescent Psychiatry 5
• Assess for paradoxical reactions, especially in children and those with developmental disabilities, when using benzodiazepines, as recommended by the Critical Care Medicine journal 6
• Taper medications gradually, especially benzodiazepines and antipsychotics, to avoid withdrawal symptoms, as recommended by the Journal of the American Academy of Child and Adolescent Psychiatry 7
• Monitor for QTc prolongation, especially with certain drug combinations, when using antipsychotics, as recommended by the Pediatrics journal 2
• Use lower doses of benzodiazepines, such as 0.25-0.5mg lorazepam, for elderly patients, as recommended by the Annals of Oncology 3

Medication Safety and Adverse Effects

• Avoid abrupt discontinuation of medications, as this may cause withdrawal symptoms including anxiety, agitation, tremors, and insomnia, as recommended by the American Academy of Child and Adolescent Psychiatry 7
• Be cautious when combining antipsychotics with other medications that may prolong QTc interval, as recommended by the Pediatrics journal 2
• Neuroleptic Malignant Syndrome (NMS) is primarily caused by severe muscle rigidity and resultant muscle damage due to dopamine receptor blockade in the central nervous system, leading to elevation of Creatine Kinase (CK) levels, according to the American Academy of Pediatrics 8

• The following criteria are used to diagnose NMS:

  Criteria	Description
  Exposure to dopamine antagonist or withdrawal of dopamine agonist	Recent use of dopamine antagonist or withdrawal of dopamine agonist
  Hyperthermia	Elevated body temperature
  Rigidity	Muscle rigidity
  Mental status alteration	Changes in mental status
  Creatine kinase elevation	Elevated creatine kinase levels
  Sympathetic nervous system lability	Autonomic instability
  Hypermetabolism	Increased metabolic rate
  Negative workup for infectious, toxic, metabolic, or neurologic causes	No evidence of underlying infection, toxicity, metabolic disorder, or neurologic condition

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• When elevated CK is detected in suspected NMS, provide IV fluids to prevent renal damage from rhabdomyolysis, and discontinue the offending antipsychotic immediately, as recommended by the American Academy of Pediatrics 8
• Consider hemodialysis if renal failure develops, and use direct-acting vasoactive agents like phenylephrine or norepinephrine for hemodynamic instability, avoiding indirect agents like dopamine in patients with NMS, as recommended by the American Academy of Pediatrics 8
• Benzodiazepines, such as diazepam or lorazepam, are recommended as first-line treatment for agitation and muscle activity reduction in NMS patients, and in severe cases with persistent symptoms, bromocriptina (dopaminergic agonist) and dantroleno (muscle relaxant) may be used, as recommended by the American Academy of Pediatrics 8
• Supportive care includes management of hydration with intravenous fluids, especially in cases of dehydration or rhabdomyolysis, as well as external cooling measures for hyperthermia and continuous cardiorrespiratory monitoring, as recommended by the American Academy of Pediatrics 8
• Young adults and males are at higher risk of developing NMS, and concomitant use of multiple psychotropics, rapid dose escalation, dehydration, and physical exhaustion are also risk factors to consider, as recommended by the American Academy of Pediatrics 8
• Patients with schizophrenia are at higher risk of thermal dysregulation compared to those with other conditions, and the American College of Psychiatry recommends considering antipsychotics with lower risk of thermal dysregulation, such as aripiprazole, when initiating treatment, especially in patients with risk factors for thermal dysregulation, as recommended by the American College of Psychiatry 3
• Wait at least 2 weeks after complete resolution of symptoms before restarting antipsychotic agents, starting with low-potency agents and gradually increasing the dose, as patients with a history of NMS have a higher risk of recurrence, according to the American Psychiatric Association and the American Academy of Pediatrics 9, 8