What is the intensity of anticholinergic side effects of lurasidone compared to other Second-Generation Antipsychotics (SGAs)?

Anticholinergic Side Effects of Lurasidone Compared to Other SGAs

Lurasidone has minimal to no anticholinergic side effects compared to other second-generation antipsychotics (SGAs), making it one of the safest options in this regard. 1, 2, 3

Receptor Binding Profile

• Lurasidone has no affinity for muscarinic M1 receptors, which are primarily responsible for anticholinergic side effects such as dry mouth, constipation, blurred vision, and cognitive impairment 2, 3
• Unlike many other SGAs, lurasidone's pharmacological profile shows minimal binding to histaminergic H1 receptors, which can contribute to sedation and anticholinergic effects 3, 4
• Lurasidone primarily acts as an antagonist at dopamine D2 and serotonin 5HT2A receptors, with high affinity for 5HT7 and 5HT1A receptors, but lacks significant affinity for receptors associated with anticholinergic effects 1, 2

Comparative Anticholinergic Burden

• First-generation antipsychotics and some SGAs (particularly clozapine, olanzapine, and quetiapine) have significant anticholinergic properties that can cause dry mouth, constipation, urinary retention, and cognitive impairment 5
• Anticholinergic effects are particularly problematic in older adults, who are more susceptible to adverse outcomes including falls, cognitive impairment, and exacerbation of conditions like glaucoma or prostatic hypertrophy 5
• Lurasidone's lack of anticholinergic activity represents a significant clinical advantage over many other antipsychotics, especially for vulnerable populations 3, 4

Clinical Implications

• The minimal anticholinergic profile of lurasidone makes it a preferred option for:

  • Elderly patients who are more sensitive to anticholinergic side effects 5
  • Patients with comorbid conditions that could be worsened by anticholinergic effects (e.g., narrow-angle glaucoma, prostatic hypertrophy, cognitive impairment) 5
  • Patients already taking other medications with anticholinergic properties 5

• Common anticholinergic side effects seen with other SGAs but rarely with lurasidone include:

  • Dry mouth and eyes 5
  • Constipation 5
  • Urinary retention 5
  • Blurred vision 5
  • Cognitive impairment 3

Side Effect Profile of Lurasidone

• Lurasidone's most common side effects are not anticholinergic in nature but include:

  • Somnolence and sedation (despite low H1 affinity) 1, 6
  • Akathisia and extrapyramidal symptoms 2, 4
  • Nausea and other gastrointestinal disturbances 6
  • Mild hyperprolactinemia 2, 4

• Lurasidone has a favorable metabolic profile with minimal weight gain and no clinically meaningful alterations in glucose or lipids 1, 6

Clinical Considerations

• Lurasidone should be administered once daily with at least 350 calories of food to optimize bioavailability 1
• The recommended starting dose is 40 mg/day with a maximum recommended dose of 80 mg/day, as higher doses may increase the risk of side effects like akathisia and somnolence without additional benefit 1
• Lurasidone is primarily metabolized through the CYP3A4 enzyme system, so concomitant use with strong inhibitors or inducers of CYP3A4 is contraindicated 1

In conclusion, when considering anticholinergic burden among SGAs, lurasidone stands out as having one of the most favorable profiles with minimal to no anticholinergic side effects, making it particularly suitable for patients at risk for or sensitive to anticholinergic adverse effects.