-Study phase was changed from Phase 4 to Phase 3b. -Estimated number of sites was increased from 75 to 150 and estimated number of patients was increased from 532 to 760 randomised. -Text was added to update MMRM model description for EQ-5D-5L endpoint. -Extrapyramidal Symptom Rating Scale–Abbreviated was removed from the safety follow-up visit. -Probabilities of observing AEs were adjusted based on the new sample size. -Text stating overdose of study drug without signs or symptoms would not be considered an AE was removed.

-Assessment of safety and tolerability described by EPS and cognition was added as secondary objective. As a result of this addition, ESRS-A and MMSE were switched from primary to secondary endpoints. -Assessment of safety and tolerability of pimavanserin as described by suicidality. was added as exploratory objective. Accordingly, C-SSRS and GCAS were switched from primary to exploratory endpoints. -Laboratory and ECG results were removed as primary endpoints but retained as safety assessments. -Repetition of ECGs at Screening or Baseline was allowed. -Sleep Disorders Inventory was added as an exploratory endpoint (Baseline, Weeks 4 and 8/EOT). -Estimated number of sites was revised to 80; estimated number of patients was decreased to 300 randomised. The probabilities of observing AEs was adjusted based on the new sample size. -Inclusion/exclusion criteria were revised to: exclude pregnant or breast feeding patients; exclude patients with severe or medically significant impairment of hepatic or renal function. Patients with stroke within 3 months before Visit 1 or history of central nervous system neoplasm or unexplained syncope were not allowed. Retesting of patients testing positive for amphetamines was allowed. -Statistical details were added, defining MMRM for change from Baseline in MMSE and ESRS-A scores and ANCOVA for EQ-5D-5L. -Mini-Mental State Examination was added to all scheduled visits; EQ-5D-5L was added to Baseline and Week 8/EOT -Pregnancy test was added at Week 8 or EOT visit. -Urine toxicity screen was removed at Baseline. -CGI–S and ESRS-A were added to unscheduled visits. CGI-I was added at Weeks 1, 2, 4, 6, and 8/EOT. -Magnesium testing was added at Screening; TSH and free T4 testing were limited to Screening.

-Specified that a serum pregnancy test should be conducted at Visit 1, and urine pregnancy tests at all subsequent visits. -Clarified process for repeating if ECGs.

-Changed indication from psychosis symptoms to neuropsychiatric symptoms. Consequently, inclusion criteria related to NPI were changed to indicate that patients were required to have at least one individual domain score greater than or equal to 4. -Inclusion criteria were revised related to reliability of the designated study partner/caregiver, the discontinuation of cholinesterase inhibitor or memantine prior to Baseline, and that MRI could be conducted instead of CT at Screening. -Exclusion criteria were revised to exclude patients with implantable cardiac defibrillator and those with history of HIV or hepatitis C infection. -Exclusion criteria were revised regarding QTcF levels allowed for patients on citalopram, escitalopram, or venlafaxine, regarding retesting of patients with prolonged QTcF, and regarding heart rate assessment in patients with bradycardia. -Clinical laboratory tests were added i.e. VLDL, absolute neutrophil count, and leukocyte esterase.

-Clarified timing of safety follow-up and definition of screening period -Extended period of AE recording for patients who rolled over into an open-label extension study -Updated TEAE definition -Specified management of cases of significant undercompliance (defined as <80% compliance) -Added temperature to vital sign measurements -Clarified description of ECG parameters, added RR interval -Clarified that unblinded interim analyses were allowed for patients who had exited the study to support safety evaluations for regulatory submissions -Clarified that lack of Medical Monitor contact does not preclude the Investigator from unblinding the patient. -Modified table of prohibited and restricted medications to better define anticholinergics, to more clearly define the washout period for anticonvulsants and mood stabilisers, and to prohibit use of methadone

-Number of study sites was updated to about 100; number of patients was updated to about 750. -Exclusion criteria were updated to exclude patients with aneurysm with a risk of rupture above threshold. -Probabilities of observing AEs were adjusted based on the new sample size. -Clarified timing of safety follow-up. -Added definitions of prior and concomitant medications. -Added a newsection describing Acadia’s quality risk management policy. -Clarified the requirements for the use of prohibited and restricted medications for esketamine and benzodiazepine use.