Behavioral and Cognitive Response to Selective Serotonin Reuptake Inhibitors in Frontotemporal Lobar Degeneration: A Systematic Review and Meta-analysis

Abstract

Objective This article systematically reviews current literature on the efficacy and efficiency of selective serotonin reuptake inhibitors (SSRIs) in the treatment of patients with frontotemporal lobar degeneration (FTLD), with a particular focus on behavior and cognitive functions. Methods A search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using CENTRAL, MEDLINE, and Cochrane Library databases. Eleven randomized controlled trials and open-label studies looking at the effects of SSRIs on FTLD patients were included. A random-effects meta-analysis was performed, consisting of 3 randomized and controlled studies that used the neuropsychiatric inventory to assess SSRI intervention. Results The meta-analysis shows a combined mean reduction of 10.17 points (95% confidence interval, 18.14–2.19; P = 0.01) on the neuropsychiatric inventory with SSRI treatment in FTLD patients. The I 2 calculated for this study was 62% (P = 0.07), which represents moderate heterogeneity among the studies. The Egger regression test (P = 0.526) did not show a publication bias. Sensitivity analysis showed no significant change. Conclusions The current meta-analysis supports SSRIs as an intervention for management of behavioral symptoms of FTLD. Marked improvements were seen in disinhibition, irritability, aggression, and aberrant motor activity across studies. However, apathy/loss of empathy did not show similarly promising results. A deteriorative effect on cognition was seen associated with SSRI use.

Successful Treatment of Inappropriate Sexual Behavior and Disinhibition in Dementia With Paroxetine

“…4 There is limited evidence that SSRIs are useful for disinhibition, irritability, aggression, and aberrant motor activity. 5 In this case, paroxetine was effective for disinhibition and ISB. The tic symptom was an aspect of repetitive behavior in BPSD or drug-induced tardive Tourette syndrome.…”

“…Antipsychotic-associated OCSs occurred in susceptible patients with schizophrenia, 2,8 bipolar disorder, 1,4 intellectual disability, 3 and delusional disorder 4 and can improve after dose reduction, drug discontinuation, adjunctive selective serotonin reuptake inhibitor (SSRI), 9 and memantine. 8 Case reports and prospective open-label studies suggest that switching 5 to or augmentation 9,10 with aripiprazole [9][10][11] and amisulpride 5 are helpful. The hypothesized mechanisms of OCSs are dysregulation of various neurotransmitter systems, particularly dopamine and serotonin, for example, hypersensitivity of 5-HT 2A Rs and 5-HT 2C Rs after chronic antagonism, 9 different medications' preferential affinity for dopamine and serotonergic receptors in the orbitofrontal cortex, 12 striatum and limbic system, 2,9 genetic susceptibility, 9 and D 2 /D 3 Rs dysregulation.…”

“…S econd-generation antipsychotics with D 2 , 5-HT 2A , and 5-HT 2C antagonistic properties can be associated with de novo obsessive-compulsive symptoms (OCSs) or exacerbate preexisting OCSs. Reported second-generation antipsychotics include clozapine, 1 olanzapine, 2 risperidone, 3 quetiapine, 4 aripiprazole, 5 and ziprasidone. 2 Cariprazine, an approved medication for the management of schizophrenia and bipolar I disorder with a partial agonism at dopamine D 2 /D 3 receptors (D 2 /D 3 Rs) and serotonin 5-HT 1A Rs as well as antagonism at 5HT 2A Rs and 5-HT 2B Rs, 6 has never been reported to be associated with OCSs.…”

“…13,14 In humans, a recent meta-analysis of imaging studies shows reduced striatal D 2 /D 3 Rs availability in medication-free patients with OCD compared with healthy participants. 15,16 In contrast, a D 2 /D 3 R partial agonist (aripiprazole) and a D 2 /D 3 R antagonist (amisulpride) can relieve antipsychotic-associated OCSs 5,[9][10][11] and OCD 17 as well as OCD in patients with bipolar disorder. 18 A meta-regression analysis of the relationship between antipsychotics' effectiveness in OCD and binding affinities to cloned dopamine and serotonin receptor subtypes revealed that only D 2 and D 3 Rs affinity was predictive for clinical response.…”

“…Nonpharmacological strategies (environmental approaches) are considered before pharmacological intervention for the treatment of behavioral and psychological symptoms of dementia (BPSD) in FTD because of a lack of solid evidence for pharmacological therapy 4 . There is limited evidence that SSRIs are useful for disinhibition, irritability, aggression, and aberrant motor activity 5 . In this case, paroxetine was effective for disinhibition and ISB.…”