None listed
Conditions
Brief summary
Breathlessness continues to be a major clinical problem for many people with advanced progressive illnesses such as cancer, end-stage cardiac failure or chronic obstructive pulmonary disease even when they are receiving the best treatment for the underlying disease. Although there are some interventions that may offer benefit (oxygen therapy, sustained release low dose morphine), there is still a need for a wider range of interventions to meet the needs of people with refractory breathlessness. Sertraline, an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, is primarily used to treat major depression as well as obsessive–compulsive, panic, and social anxiety disorders. Previous research has suggested that treatment of concomitant mood or anxiety symptoms can improve dyspnoea however studies are needed to further clarify its potential benefits for the treatment of breathlessness. The research team has conducted a Phase II double blind, titrated dose, multi-site placebo controlled pilot study of sertraline (ACTRN12608000253303) using the proposed inclusion and exclusion criteria and the measures proposed in this study design. The pilot study has demonstrated acceptability and feasibility of this study, however further Phase III data is needed in order to ensure that this is a well tolerated and effective intervention suitable for a broad range of people with refractory breathlessness. This study will evaluate critically a new but theoretically useful therapy whose role needs to be carefully defined. Although sertraline has been used in small uncontrolled studies, the evidence for a net clinical benefit is inadequate. Aim: The primary aim is to test the efficacy of sertraline compared with placebo in relieving the sensation of intractable breathlessness. Secondary aims focus on the impact of the sertraline on improving quality of life (QOL), dyspnoea-related anxiety and depression, adverse effects, function and clinical predictors of benefit.
Interventions
Sertraline/placebo 25-100mg in the morning via oral capsule.
Days 1-3 Sertraline/placebo 25mg each morning, Days 4-6, sertraline/placebo 50mg each morning, Days 7-28 sertraline/placebo 100mg each morning. Dose modification is included in the protocol. After the 28 day intervention period the dose is titrated downwards with the medication ceasing after day 34, or, participant can remain on blinded medication if experiencing benefit from the medication.
Sponsors
Flinders University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Adults (age >18) Refractory dyspnoea where the underlying cause of the dyspnoea has been maximally treated. Refractory dyspnoea does not have a minimum duration and can have been present for any period of time. A medical specialist must document that all identified reversible causes of the dyspnoea are being optimally managed Breathlessness of a level 3 or higher on the Modified Medical Research Council (MRC) dyspnoea scale On stable medications for breathlessness over the prior week except routine “as needed” medications Prognosis of at least 2 months in the opinion of the treating clinician English-speaking and able to read study questionnaires (5th grade level) Able to provide informed consent
Exclusion criteria
1. Previous adverse reaction to sertraline 2. History of severe hepatic impairment defined as Childs Pugh Class of ‘C’ (score of 11 to 15) 3. Gastro-intestinal bleeding within the previous six months 4. Serum sodium less than 128mmol/l 5. Recent difficulty with seizure control 6. Evidence of respiratory depression with resting respiratory rate <8 7. Active respiratory or cardiac event in the previous week, not including upper respiratory tract infections. Illness must be resolved for at least 1 week prior to baseline evaluation, as judged by a doctor involved in the care of the person 8. Documented previous respiratory failure induced by any opiate medication 9. Pregnant or breastfeeding 10. Unable to give informed consent or complete diary entries 11. Depressive symptomology or suicidality (HADS depression subscale >16) 12. Current therapy with any one of the following medications due to the risk of serotonin syndrome: any selective serotonin reuptake inhibitor (SSRI); any serotonin-norepinephrine reuptake inhibitor (SNRI); noradrenergic and specific serotonergic antidepressant (NaSSA); any serotonin receptor agonist; any tricyclic antidepressant; any monoamine oxidase inhibitor (MAOI) or who have been taking non-reversible monoamine oxidase inhibitors within 4 weeks prior to study entry or reversible MAOIs within 2 days of study entry; Buspirone; Lithium; Carbamazepine; Linezolid; Imatinib; Amphetamine type drugs (dexamphetamine, methylphenidate); Weight loss drugs (phenteramine, diethylpropion, sibutramine); Over the counter medications (dextromethorphan, chlorpheniramine, and bropheniramine); Complementary medicines- St Johns Wort, tryptophan, S-adenosyl-methionine (SAME);
Outcome results
None listed