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Alternative Treatment Approaches
to Agitation and Depression
in the Elderly

Advancing Precision Medicine
in Psychiatry

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Alternative Treatment Approaches to Agitation
and Depression in the Elderly
Dr. Nabil Kotbi
  Dr. Nabil Kotbi

“To say a patient is agitated means nothing if you don’t assess its cause,” says Nabil Kotbi, MD, a geriatric psychiatrist and Unit Chief of The Haven and the Addiction and Recovery Unit at NewYork-Presbyterian/Westchester Division. “Agitation is a common but challenging complication of Alzheimer’s and related disorders. In the elderly, you’re generally dealing with co-morbid conditions in addition to a neurodegenerative illness. So before we reach for an antipsychotic agent as the first-line treatment for agitation, we need to have a complete picture of the patient and any factors that may have precipitated the agitation.

“For example,” says Dr. Kotbi, “someone with Lewy body dementia will have an exquisite sensitivity to an antipsychotic. Or perhaps a patient with Alzheimer’s has a specific nurse who comes at particular times. That is what anchors them. Then suddenly, that nurse is gone. The loss of that anchor could have caused the individual to become agitated. In these cases an antipsychotic medication will not address the real issue. Is this the failure of the antipsychotic or is it a failure to understand that patient’s baseline – a medical problem, environmental trigger, poor sleep, delirium, or depression?

“The idea that antipsychotics are always the first-line treatment is not necessarily true,” continues Dr. Kotbi. “A National Institute of Mental Health study in 2002 looking at the efficacy of an antipsychotic compared to SSRIs to treat agitation in patients with dementia showed no difference and, in fact, the researchers found that the SSRIs might work better.”

According to Dr. Kotbi, despite this finding, antidepressants received limited attention in the treatment of agitation of dementia. A more recent study showed that the SSRI citalopram had equal efficacy to risperidone in the treatment of demented patients who required psychiatric inpatient care because of agitation. In a case report published in the Journal of Neuro-psychiatry and Clinical Neuroscience, Dr. Kotbi and his colleagues reviewed the use of citalopram to treat two non-depressed patients with dementia presenting with agitation
and delusions who had failed several trials of antipsychotics.

Case Study 1: An 84-year-old woman with Alzheimer’s/vascular dementia was acutely hospitalized because of physical aggression and somatic delusion. Trials of risperidone, haloperidol, and quetiapine led to equivalent response, while lorazepam worsened her agitation. Risperidone was replaced with citalopram 10 mg twice daily and increased to
15 mg twice daily. Within 72 hours, the agitation diminished dramatically, and the patient
was discharged soon thereafter. On follow-up several weeks later she remained in good behavioral control.

Case Study 2: An 80-year-old woman with Alzheimer’s dementia presented with violent behavior and paranoia. She had failed trials of atypical and typical antipsychotics. She was initially treated with risperidone but showed no improvement. She was switched to citalopram 10 mg twice daily, which was later increased to 15 mg twice daily. Her agitation and paranoia improved four days after starting citalopram and she remained agitation free throughout the hospitalization and several weeks after discharge.

“Combined with earlier studies,” says Dr. Kotbi, “this suggests that citalopram, which does not share the adverse side effects of antipsychotic agents, may be a reasonable treatment option for these patients.”

A PATH to Better Treatment
In elderly patients with major depressive disorder further complicated by cognitive impairment up to the level of moderate dementia, treatment with antidepressants has had limited success and psychosocial interventions have not been adequately explored. Researchers at NewYork-Presbyterian/Westchester investigated Problem Adaptation Therapy (PATH), a novel psychotherapy delivered in the home designed to decrease depression in adults with this combination of disorders. “Our study sought to determine the effect of this approach on regulating emotions and reducing the negative impact brought on by behavioral and functional limitations as compared to supportive therapy for cognitively impaired patients,” says Dr. Kotbi. “PATH integrates problem-solving with compensatory strategies, changes in the patient’s environment, and participation by the caregiver and incorporates the distinguishing factor of the therapy taking place in the home over a 12-week period.”

The team hypothesized that PATH participants would have greater reduction in depression and disability than those receiving supportive therapy. They also compared remission rates, time to remission, and patient and caregiver satisfaction, as well as the effects of treatment on pharmacotherapy-resistant depression.

The researchers found that PATH reduced depression and disability more than supportive therapy and that pharmacotherapy has limited effectiveness. Reductions in depression and disability were both statistically and clinically significant. “This is the first randomized trial, to our knowledge, of a psychosocial intervention for older adults living in the community with major depressive disorder and cognitive impairment, of which more than half had dementia,” says Dr. Kotbi. “The study strongly indicates that PATH may provide significant relief to this underserved population and their families.”


Reference Articles
Kotbi N, Singh A, Kneifati-Hayek J, Odom A, Alexopoulos G. Citalopram in agitated and delusional demented patients
who failed treatment with antipsychotic agents. Journal of Neuropsychiatry and Clinical Neuroscience. 2014 Apr 1;26(2):E62.

Kiosses DN, Ravdin LD, Gross JJ, Raue P, Kotbi N, Alexopoulos GS. Problem adaptation therapy for older adults with major depression and cognitive impairment: a randomized clinical trial. JAMA Psychiatry. 2015 Jan;72(1):22-30.

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