Baseline Study Characteristics

One trial enrolled 215 participants with probable or possible CATD defined by the clinical criteria of the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders (NINCDS-ADRDA), and depression defined by Cornell Scale for Depression in Dementia (CSDD) score ≥8.³⁶⁸ All participants were receiving old-age psychiatry services from UK National Health Service centers and 14 percent lived in care homes. Mean participant age was 79 years, and 70 percent were female. Mean Mini-Mental State Exam (MMSE) score was 18.0, suggesting mild to moderate CATD severity. Mean Neuropsychiatric Inventory (NPI) and CSDD scores were 28.4 and 12.6, respectively. Participants were randomized to sertraline up to 150 mg/day or mirtazapine 45 mg/day for 39 weeks for treatment of depression. Appendix J provides detailed evidence tables, summary ROB assessments, and strength of evidence for key comparisons and outcomes.

Outcomes

Table 11.1 summarizes primary comparative effectiveness and harms outcomes. For comparative effectiveness, evidence was insufficient to draw conclusions about differences between sertraline and mirtazapine for depression, general behavior, or quality of life, and no data were reported for agitation, aggression, psychosis or disinhibited sexual behavior at 2 weeks or longer, or for anxiety at 24 weeks or longer. For caregiver outcomes, sertraline and mirtazapine did not statistically differ at 39 weeks for caregiver burden³⁸³ (standardized mean difference [SMD], 0.21 [95% confidence intervals (CI), ‑0.11 to 0.54]), caregiver general health questionnaire (GHQ-12) (SMD, 0.22 [95% CI, ‑0.11 to 0.55]), caregiver general quality of life mental component score (SF-12 MCS) (SMD, 0.04 [95% CI, ‑0.29 to 0.37]), or caregiver general quality of life physical component score (SF-12 PCS) (SMD, ‑0.12 [95% CI, ‑0.45 to 0.21]).³⁶⁸

For harms, evidence was insufficient to draw conclusions about differences between sertraline and mirtazapine for serious adverse events. Five deaths were reported for each treatment group, but no studies reported data on withdrawals due to adverse events, somnolence, confusion, falls, extrapyramidal symptoms or stroke.

Table 11.1

Summary of findings for primary outcomes: sertraline versus mirtazapine.

Variation in Outcomes by Participant or Drug Characteristics

Efficacy findings were reported to not differ in subgroup analyses stratified by baseline depression severity (CSDD score 8 to 11 vs. ≥12).³⁶⁸ No studies reported whether differences in treatment efficacy and harms between sertraline and mirtazapine varied as a function of participant characteristics or drug dose, duration, or delivery route.

Baseline Study Characteristics

One trial enrolled 199 participants with probable or possible CATD defined by NINCDS-ADRDA clinical criteria who were living in care homes in the UK or Norway and already were receiving an antipsychotic. ³³¹ Mean participant age was 83 years, and 69 percent were female. Mean MMSE score was 8, suggesting moderate to severe CATD. Mean NPI and Cohen-Mansfield Agitation Inventory (CMAI) scores were 17.6 and 51.4, respectively. Participants were randomized to antipsychotic continuation (risperidone 0.5 mg, olanzapine 5 mg, quetiapine 50 mg, or haloperidol 0.5 mg, once or twice daily as needed) or memantine (10-20 mg/day) for 24 weeks.

Outcomes

Table 11.2 summarizes primary comparative effectiveness and harms outcomes. For comparative effectiveness, evidence was insufficient to draw conclusions about differences between memantine and antipsychotics for agitation or general behavior, and no data were reported for aggression, psychosis or disinhibited sexual behavior at 2 weeks or longer, or for depression or anxiety at 24 weeks or longer.

For harms, evidence was insufficient to draw conclusions about differences between memantine and antipsychotics for serious adverse events. In the memantine group, there were no strokes and 9 percent of participants died, compared to the antipsychotic group with 2.5 percent incidence of stroke and 4 percent mortality. No studies reported data on withdrawals due to adverse events, somnolence, confusion, falls or extrapyramidal symptoms.

Table 11.2

Summary of findings for primary outcomes:* memantine versus antipsychotics.

Variation in Outcomes by Participant or Drug Characteristics

No studies reported data on whether comparative effectiveness and harms between memantine and antipsychotics varied as a function of patient characteristics, or drug dose, duration, or delivery route.