Research Updates: Alzheimer’s Disease and Antidepressants

Age-Related Health Problems

Glen Spielmans, PhD, has disclosed that he has no relevant financial or other interests in any commercial companies pertaining to this educational activity.

Citalopram May Help with Agitation in Alzheimer’s Disease

Agitation is common in Alzheimer’s disease (AD), and while antipsychotics are frequently given for agitation, they can also increase risk for cardiac and cerebrovascular events. What to do? A group of researchers recently investigated the possibility that an antidepressant, citalopram (Celexa), may be an alternative choice.

The Citalopram for Agitation in AD Study (CitAD) was a randomized, placebo-controlled, double-blind study of 186 patients with Alzheimer’s disease and clinically significant agitation. All participants received a psychosocial intervention, consisting of counseling sessions, educational materials, and 24-hour crisis management. Investigators measured levels of agitation as well as overall function and cognitive and physical safety.

Participants were randomized to either citalopram (n=94) or placebo (n=92) for a nine-week trial. They were permitted to continue taking cholinesterase inhibitors and/or memantine for AD, but no other psychiatric medications. (Lorazapam and trazodone were permitted as “rescue” mediations when needed.) Patients with depression or psychosis requiring treatment with an antipsychotic were excluded from this study.

Citalopram doses were titrated from 10 mg/day up to 30 mg/day during the first three weeks as tolerated. In the final analysis, those who received citalopram showed significant improvement in the main outcome measures, the 18-point Neurobehavioral Rating Scale agitation subscale (NBRS-A) and the modified Alzheimer’s Disease Cooperative Study- Clinical Global Impressions of Change (mADCS-CGIC).

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At nine weeks, participants in the citalopram group had an average NBRSA score of 4.1, and those in the placebo group, 5.4 (p=.01) (higher scores indicate more agitation). Similarly, 40% of participants taking citalopram improved from baseline on the mADCS-CGIC, versus 26% of the placebo group.

On the other hand, citalopram was correlated with cognitive worsening in comparison to placebo (-1.05 points on the MMSE, 95% CI, -1.97 to -0.13; p=.03). There were more falls (3.4% vs. 0%) and upper respiratory tract infections (18.9% vs. 10.5%) in participants taking citalopram, but these were not statistically significant.

Other SSRI side effects were no more common with citalopram than with placebo, except for diarrhea (27.8% vs. 14.0%). Interestingly, the FDA advisory about high citalopram doses causing QTc prolongation was announced while this study was being conducted (August 2011). As a result, the investigators immediately initiated a stricter ECG monitoring protocol. ECG data were available for 48 participants; citalopram was associated with an average 18.1 ms increase in QTc vs. placebo (p=.004), and three participants taking citalopram had clinically significant QTc prolongation (>450 ms for men, >475 ms for women) compared to one taking placebo.

TCPR’s Take: The reason why citalopram might help agitation in AD is unclear, and while this study suggests that citalopram significantly reduces agitation relative to placebo, its side effects included mildly reduced cognition and QTc prolongation. Further research should help determine which patients are more likely to respond to citalopram, and whether benefits persist beyond the nine weeks of this trial. The authors also plan to study lower doses of citalopram to determine whether the FDA’s lower limit of 20 mg/d limits the benefit of this intervention.

Non-Physical Adverse Effects of ADs May Be Underreported

All antidepressants have the potential to cause physical adverse effects, such as dry mouth, drowsiness, and dizziness. But patients often report psychological and interpersonal effects, too, and the fear of these adverse reactions sometimes leads patients to refuse these drugs.

How common are non-physical side effects, such as apathy and feelings of detachment? To find out, researchers in New Zealand created an online survey and invited patients who had been prescribed antidepressants at any time during the last five years. The questionnaire featured 47 questions, inquiring about 20 biological, emotional, and interpersonal adverse effects of these medications.

Eight of the 20 effects analyzed were reported by more than half of the 1,829 participants. These included sexual difficulties (62.3%), feeling emotionally numb (60.4%), failure to reach orgasm (59.5%), drowsiness (57.8%), dry mouth (57.6%), weight gain (56.4%), “withdrawal effects” (54.9%), and “feeling not like myself” (52.4%).

A slight majority (52%) reported taking antidepressants for three or more years. SSRIs were the most widely prescribed, with smaller percentages reporting tricyclics and SNRIs. About two-fifths (39%) reported multiple antidepressants, and most respondents (83.6%) received prescriptions from a general practitioner.

Some symptoms were often identified as more severe than others. In particular, “feeling emotionally numb” was rated as moderate or severe by 35.5% of participants, while 29% reported moderately or severely “not feeling like myself.” Sexual difficulties (unspecified) and failure to reach orgasm were reported as moderate or severe by 39.1% and 40.7% of participants, respectively. Young people (18 to 25 years old) reported the greatest incidence of emotional numbness, not feeling like oneself, and suicidality.

Unpleasant side effects were reported as the reason for discontinuing medication by 47.5% of the respondents who were “not currently taking medication.” Despite the high frequency of adverse reactions, the majority (82.8%) reported that antidepressants had “reduced their depression” and half (49.2%) reported that their quality of life was “greatly improved” while taking antidepressants, although these respondents were also less likely to report adverse effects (Read J et al, Psychiatry Res 2014;2016:67–73).

TCPR’s Take: While emotional and other non-physical side effects sometimes do occur in patients who take antidepressants, the present research does little more than shed a sliver of light on an unfortunately poorly studied area. Recruiting subjects via “media releases, interviews with the researchers, and advertisements” to an internet survey is likely to attract a self-selected population of subjects who have had poor experiences with medication. That said, the high rate of adverse events cannot be solely attributed to those with an axe to grind, as only 8.2% reported having a reduced quality of life while on antidepressants. Informing patients about potential emotional and psychological effects of antidepressants is important, but the frequency.

Research Updates: Alzheimer’s Disease and Antidepressants

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This article was published in print May 2014 in Volume:Issue Volume 12, Number 5.


APA Reference
Psych Central. (2015). Research Updates: Alzheimer’s Disease and Antidepressants. Psych Central. Retrieved on August 13, 2020, from


Scientifically Reviewed
Last updated: 5 Jun 2015
Last reviewed: By John M. Grohol, Psy.D. on 5 Jun 2015
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