UWL: Association With Outcomes (2009)
- The main objective was to compare weight outcomes at six months among users of three different antidepressant groups with a control group of non-antidepressant users
- A secondary objective was to determine whether antidepressant selection was associated with weight pattern before drug initiation, to capture possible prescribing bias that would affect study inferences.
- Initial sample consisted of subjects who were not on an antidepressant at facility admission but showed antidepressant usage on subsequent assessments
- From this group, only antidepressant users who started an antidepressant after admission and remained on the same single agent for at least six months (180±30 days) were retained
- Residents not receiving an antidepressant were included as controls
- Age 65 and older.
- Age less than 65 years
- History of institutional treatment for mental retardation or developmental disability
- History of institutional psychiatric care, special treatments (dialysis, chemotherapy, radiation therapy, tracheostomy, transfusion, mechanical ventilation), parenteral nutrition, feeding tube, syringe feeding, explicit terminal diagnosis, human immunodeficiency virus infection or tuberculosis
- Subjects on two or more antidepressant groups were excluded in order to isolate the weight effect of one drug group
- Subjects on amitriptyline and trazodone were excluded because of frequent use for non-depression purposes.
Data from 1994 to 1997 were examined using the MDS+. Before data analysis, all antidepressant national drug codes were filtered by a series of decision rules to overcome inconsistent entry of these codes into the MDS+ data fields.
Retrospective cohort study using the Minimum Data Set-Plus (MDS+).
- Proportions of subjects with clinically important loss and gain and mean weight changes were compared across the four groups using chi-square tests
- Odds ratios and 95% confidence intervals were determined for the likelihood of clinically important loss and gain for each drug group compared with the none group
- Logistic regression models were used to control for age, gender, baseline weight, confounding comorbidity and functional variables related to eating
- Previous weight patterns (loss, gain, neither or unknown) before antidepressant initiation were compared across drug groups
- Mean weight changes were compared for the groups using a parametric ANOVA procedure, employing a Tukey-Kramer adjustment method to control the type I experimental error rate for all pairwise comparisons
- An expanded linear model was employed using the same potentially confounding variables to examine the impact of drug group on individual weight changes in pounds
- For the question of prescribing bias, a chi-square statistic was used to compare the distribution of subjects in the four previous weight trend categories into the various drug groups.
Timing of Measurements
Data from 1994 to 1997 were examined using the MDS+. Weight changes from baseline to six months were examined.
Weight outcomes: Rates of clinically important loss and gain (assigned for a 10% change from baseline weight or presence of the significant loss or gain markers on the six-month MDS assessment) and mean weight changes.
Antidepressant use was identified by drug code data and divided into four groups for analysis: Tricyclic depressants, selective serotonin reuptake inhibitors, others and none.
- Baseline weight
- Confounding comorbidity
- Functional variables related to eating.
- Initial N: 4,644 subjects had remained on the same antidepressant for six months
- Attrition (final N): 1,157 antidepressant users, 4,852 non-users after exclusion criteria applied. 76% female.
- 8% were 65 to 74 years
- 34% were age 75 to 84 years
- 59% were age 85 years or more.
Adjusted Mean Weight Changes over Six Months by Antidepressant Group and Pairwise Comparisons
|Changes in Pounds|
|Pairwise Differences in Weight Changes||P-value|
|None vs. TCA||0.8651|
|None vs. SSRI||0.0151|
|None vs. Other||0.2481|
|TCA vs. SSRI||0.0464|
|TCA vs. Other||0.1658|
|SSRI vs. Other||0.9591|
- Clinically important weight loss and gain occurred at six months in 14.7% and 14.4% of the sample, respectively
- In adjusted analyses, an increased likelihood of loss was found for users of selective serotonin reuptake inhibitors (odds ratio, 1.57; confidence interval, 1.30 to 1.90) and others (odds ratio, 1.89; confidence interval, 1.18 to 3.03), compared with none
- In logistic models accounting for potential confounding factors, however, selective serotonin reuptake inhibitor use showed a modest association with gain (odds ratio, 1.31; confidence interval, 1.01 to 1.70) and a trend toward a similarly modest association with loss (odds ratio, 1.28; confidence interval, 0.995 to 1.64)
- Tricyclic antidepressant use was not associated with weight gain
- When weight was examined as a continuous variable, all groups demonstrated a broad range of both loss and gain with mean-unadjusted weight changes less than three pounds
- Pairwise comparisons of adjusted differences in weight change at six months for selective serotonin reuptake inhibitors (mean loss of 1.6 pounds) and tricyclic antidepressants (mean gain of 0.4 pounds) were of marginal importance (P=0.046) given the large sample size
- No evidence was found for prescribing bias based on prior weight pattern.
Tricyclic antidepressants do not facilitate weight gain more than other antidepressant groups and selective serotonin reuptake inhibitors are not associated disproportionately with weight loss when other important clinical variables are accounted for. Small but statistically significant differences in mean weight changes between groups are largely a reflection of large sample size rather than clinically important differences. Clinicians may wish to reconsider the widely held notions that tricyclic antidepressants facilitate weight gain and that selective serotonin reuptake inhibitors place depressed older nursing facility residents at disproportionate risk for weight loss.
|University/Hospital:||Research Institute, University of Kansas Medical Center|
Subjects on several antidepressants, trazodone or amitriptyline, were excluded from analysis. Subjects were only from nursing homes in Kansas. Authors note the following limitations:
- Drug indication could not be ascertained
- Dose-response relationships could not be studied
- Only persons who remained on their initial antidepressant for at least six months were included; any possible weight-related reasons for earlier discontinuation could not be ascertained
- The other group included diverse drugs with heterogeneous chemical structures and mechanisms of action that did not fit into other categories
- Persons who received more than one agent at a time were excluded in order to isolate the weight effects of single drug groups
- Drug groups were unequal in size.
Quality Criteria Checklist: Primary Research
|1.||Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)||N/A|
|2.||Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?||Yes|
|3.||Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?||Yes|
|4.||Is the intervention or procedure feasible? (NA for some epidemiological studies)||N/A|
|1.||Was the research question clearly stated?||Yes|
|1.1.||Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?||Yes|
|1.2.||Was (were) the outcome(s) [dependent variable(s)] clearly indicated?||Yes|
|1.3.||Were the target population and setting specified?||Yes|
|2.||Was the selection of study subjects/patients free from bias?||???|
|2.1.||Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?||Yes|
|2.2.||Were criteria applied equally to all study groups?||N/A|
|2.3.||Were health, demographics, and other characteristics of subjects described?||Yes|
|2.4.||Were the subjects/patients a representative sample of the relevant population?||???|
|3.||Were study groups comparable?||???|
|3.1.||Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)||Yes|
|3.2.||Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?||???|
|3.3.||Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)||Yes|
|3.4.||If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?||???|
|3.5.||If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)||N/A|
|3.6.||If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?||N/A|
|4.||Was method of handling withdrawals described?||Yes|
|4.1.||Were follow-up methods described and the same for all groups?||Yes|
|4.2.||Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)||Yes|
|4.3.||Were all enrolled subjects/patients (in the original sample) accounted for?||Yes|
|4.4.||Were reasons for withdrawals similar across groups?||N/A|
|4.5.||If diagnostic test, was decision to perform reference test not dependent on results of test under study?||N/A|
|5.||Was blinding used to prevent introduction of bias?||Yes|
|5.1.||In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?||N/A|
|5.2.||Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)||Yes|
|5.3.||In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?||Yes|
|5.4.||In case control study, was case definition explicit and case ascertainment not influenced by exposure status?||N/A|
|5.5.||In diagnostic study, were test results blinded to patient history and other test results?||N/A|
|6.||Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?||Yes|
|6.1.||In RCT or other intervention trial, were protocols described for all regimens studied?||Yes|
|6.2.||In observational study, were interventions, study settings, and clinicians/provider described?||N/A|
|6.3.||Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?||Yes|
|6.4.||Was the amount of exposure and, if relevant, subject/patient compliance measured?||No|
|6.5.||Were co-interventions (e.g., ancillary treatments, other therapies) described?||Yes|
|6.6.||Were extra or unplanned treatments described?||N/A|
|6.7.||Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?||N/A|
|6.8.||In diagnostic study, were details of test administration and replication sufficient?||N/A|
|7.||Were outcomes clearly defined and the measurements valid and reliable?||Yes|
|7.1.||Were primary and secondary endpoints described and relevant to the question?||Yes|
|7.2.||Were nutrition measures appropriate to question and outcomes of concern?||Yes|
|7.3.||Was the period of follow-up long enough for important outcome(s) to occur?||N/A|
|7.4.||Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?||Yes|
|7.5.||Was the measurement of effect at an appropriate level of precision?||Yes|
|7.6.||Were other factors accounted for (measured) that could affect outcomes?||Yes|
|7.7.||Were the measurements conducted consistently across groups?||N/A|
|8.||Was the statistical analysis appropriate for the study design and type of outcome indicators?||Yes|
|8.1.||Were statistical analyses adequately described and the results reported appropriately?||Yes|
|8.2.||Were correct statistical tests used and assumptions of test not violated?||Yes|
|8.3.||Were statistics reported with levels of significance and/or confidence intervals?||Yes|
|8.4.||Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?||N/A|
|8.5.||Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?||Yes|
|8.6.||Was clinical significance as well as statistical significance reported?||Yes|
|8.7.||If negative findings, was a power calculation reported to address type 2 error?||N/A|
|9.||Are conclusions supported by results with biases and limitations taken into consideration?||Yes|
|9.1.||Is there a discussion of findings?||Yes|
|9.2.||Are biases and study limitations identified and discussed?||Yes|
|10.||Is bias due to study's funding or sponsorship unlikely?||Yes|
|10.1.||Were sources of funding and investigators' affiliations described?||Yes|
|10.2.||Was the study free from apparent conflict of interest?||Yes|