Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia

• Status: Completed
• Trial end date: 2009-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Frontotemporal lobar degeneration(FTLD) is a common cause of early-onset dementia. FTLD is characterized multiple behavioral symptoms including mental rigidity, irritability, emotional blunting, disinhibition, apathy, and aggression. These behavioural disturbances are particularly important because they increase caregiver burden and may lead to earlier institutionalization. While the causes of FTLD are largely unknown, there is a great deal of evidence suggesting that a brain chemical called serotonin regulates many of the behaviours that are disturbed in FTLD. Our objective is therefore to determine whether dysfunction in the brain's serotonin system is responsible for behavioural problems among FTLD patients. We hope to take the first steps towards a scientific understanding of the behavioural symptoms of FTD, and use our findings to support a larger study optimizing the treatment of targeted behavioural disturbances in FTLD using the antidepressant citalopram.

Citalopram increases transmission by serotonin; we plan to use this medication to determine whether there are any differences in how the serotonin system functions in FTLD patients who display different levels of behavioural disturbances. Patients will be given citalopram and will have their blood drawn after 2 and 3 hours to determine plasma levels of the hormones cortisol and prolactin at those times. These hormones are good indicators of serotonergic functioning in the central nervous system.

We expect that patients with lower levels of serotonergic functioning will have more severe behavioural disturbances and be less responsive to treatment with citalopram. Following their first test day, we will provide patients with a 6-week supply of citalopram, and assess them for any changes in behaviour at the end of this treatment.

This study aims to obtain a better understanding of how changes in the serotonin system relate to behavioural symptoms in FTLD patients. Using the information from this pilot study, we can plan a larger study to determine whether certain behaviours will respond to treatment with citalopram, and if so, determine whether it is possible to predict which patients, based on individual characteristics, are most likely to respond to this treatment. This methodology will therefore not only provide a scientific rationale for treatment of FTLD, but also provide guidance for ongoing, individualized therapy.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sunnybrook Health Sciences Centre
• Collaborator: Alzheimer Society of Canada
• Treatments: Citalopram

Criteria

Inclusion Criteria:

• Meet the DSM-IV criteria for primary degenerative dementia

• Meet standard clinical criteria for frontotemporal dementia (ie., frontotemporal degeneration including both the frontal/behavioural variant and primary progressive aphasia)

• Have significant behavioural problems as demonstrated by a score of at least eight on the Neuropsychiatric Inventory (NPI) an

• An independent clinical decision to receive psychotropic medication for behavioural disorders

Exclusion Criteria:

• An abnormal biochemical screening (blood cell count, vitamin B12 or thyroid function tests)

• Significant medical illness or other medical/neurological conditions which diminish cognitive function (including: drug overdose, severely disturbed liver, kidney, lung or heart function, anemia, hypothyroidism, vitamin B12 or folic acid deficiency, syphilis, uncontrolled diabetes, Parkinson's disease, Huntington's chorea, progressive supranuclear paralysis, brain tumour, subdural hematoma, multiple sclerosis, or brain trauma);

• An Hachinski ischemic score ≥444;

• Electrocardiographic, laboratory or physical evidence of significant cardiovascular disease;

• Hypertension >160 mmHg systolic or >100 mmHg diastolic;

• A brain computed tomographic scan that could not be interpreted as consistent with FTLD;

• Presence of premorbid or current psychiatric diagnosis (including: major depression, schizophrenia, psychotic symptoms of a severity likely to provoke violent or dangerous behaviour such as command hallucinations to harm people or persecutory delusions that provoke violent reactions, psychoactive substance abuse or dependence);

• Contraindications to receiving citalopram (such as concomitant MAOI or within 2 weeks, or hypersensitivity to citalopram); or

• Ongoing need for psychotropic medications (i.e., unsuitable for washout) or administration of a depot antipsychotic injection within one treatment cycle of visit 1