Hardy BG, Shulman KI, Zucchero C. Gradual discontinuation of lithium augmentation in elderly patients with unipolar depression. Journal of Clinical Psychopharmacology 1997;17:22-26
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/9004053
| Methods | Study design: Randomized double-blind placebo-controlled study with parallel-design
Number of groups: Two groups |
| Participants | Number of participants: 12 randomized, 9 completed
· Active deprescribing group: 6 randomized, 4 completed · Control group: 6 randomized, 5 completed Age: 79 ± 6 years Sex: 10 female, 2 male Inclusion criteria: · 65 years and older · Meet DSM-III-R diagnostic criteria for major unipolar depressive episode before antidepressant therapy was initiated · Refractory to antidepressant therapy · Without depressive symptoms for at least 1 year while maintained on lithium augmentation · Without change in antidepressant dose for at least 1 year while maintained on lithium augmentation · Demonstrated responsiveness to lithium augmentation · Score <20 on Geriatric Depression Rating Scale for self-assessment depression rating score · Score <15 on Montgomery-Ashberg Depression Rating Scale from interview · Score >20 on MMSE score · Score > 8 on lithium withdrawal attitude questionnaire Exclusion criteria: · Dementia · Suicidal tendencies · History of severe symptoms with relapse · General overall health contraindicated study participation (in the opinion of the investigators) Concurrent medicine: All participants were on a tricyclic antidepressant and lithium Country: Canada Setting: Community – geriatric out-patient clinic |
| Interventions | Medicine: Lithium
· Prescribed lithium for 6.3 ± 3.6 years before enrollment in the study · Mean baseline lithium levels 0.4 ± 0.1 Withdrawal schedule: Withdrawn 150mg daily each week in the withdrawal group until completely replaced with matching placebo Comparator: Placebo compared to continued treatment |
| Outcomes | Serum creatinine
Serum thyroid-stimulating hormone Mean composite side effect symptom scores Depression |
| Dates | Dates: July 1991 start
Follow-up duration: 24 months |
| Funding sources | Sunnybrook Trust for Medical Research |
| Notes |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Low risk | “A prospective, double-blind, placebo-controlled, parallel-design withdrawal study.” “Treatment assignment was determined from a list of computer-generated random-numbers. “ |
| Allocation concealment (selection bias) | Low risk | Probably done, but not explicitly described. It is stated that allocation was concealed, but method is not described: “Neither the patient nor the investigators involved in-patient assessment were aware of the study assignments.””A record of the drugs dispensed and returned, as well as the study randomization code, was maintained by the out-patient psychiatry pharmacy.” |
| Blinding of participants and personnel (performance bias) | Low risk | “A prospective, double-blind, placebo-controlled, parallel-design withdrawal study.” “To maintain the study blind, actual (active) and fabricated (placebo) lithium levels were returned to the primary investigator after each clinic visit. Lithium was withdrawn slowly (maximum 150 mg/day/week) in the withdrawal group until the augmentation therapy was completely replaced with matching placebo. All patients returned for scheduled visits at approximately the same time on each clinic day and returned any study medications for compliance assessment (capsule counts).” |
| Blinding of outcome assessment (detection bias) | Low risk | As above |
| Incomplete outcome data (attrition bias) | High risk | The study reports on those who dropped out, but the analysis is as-treated.
Some outcomes reported as “significant difference at p< 0.05” with actual values not stated, only change. |
| Selective reporting (reporting bias) | Low risk | Pre-specified study protocol not available, but the stated objectives are reported. |
| Other bias | Low risk |
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