Lofepramine Hydrochloride

To investigate the association between antidepressant prescribing and the rate of insulin initiation in type 2 diabetes.

Using UK primary care records we completed a nested-case control study in a individuals with comorbid depression and type 2 diabetes. Cases were defined as individuals initiating insulin, controls were individuals remaining on oral antidiabetic medication. We used conditional logistic regression to estimate incident rate ratios (IRR) and the 95% confidence intervals (CI) for the association between antidepressant prescribing and initiating insulin. We adjusted for demographic characteristics, comorbidities, health service and previous medication use.

We included 11,862 cases who initiated insulin, and 43,452 controls. Increased rates of insulin initiation were associated with any antidepressant prescription (IRR 3.78, 95% CI 3.53-4.04), longer (24+ months) durations of antidepressant treatment (IRR 5.61, 95% CI 5.23-6.03), and higher numbers (3+) of different antidepressant agents prescribed (IRR 5.72, 95% CI 5.25-6.24). There was no difference between recent and non-recent antidepressant prescriptions, or between different antidepressant agents.

Antidepressant prescribing was highly associated with the initiation of insulin therapy. However, this may not indicate a direct causal effect of the antidepressant medication itself, and may be a marker of more severe depression influencing diabetic control.

Tricyclic antidepressants (TCAs) remain widely prescribed for depression and many other conditions. There may be important differences between individual TCA in regard to their overdose toxicity and their cardiac toxicity in clinical use. We conducted a systematic review to compare the toxicity of individual TCA in overdose and the risk of serious adverse cardiac events occurring with therapeutic doses. We used the fatal toxicity index (FTI) and case fatality ratio as markers of fatality in overdose, and hazard ratios or odds ratios for the risk of cardiovascular adverse events during normal clinical use. In all, 30 reports of mortality in overdose and 14 observational studies assessing the risk of cardiovascular adverse events in clinical use were included. FTI values were of the same order of magnitude (101–102) for all TCAs except lofepramine. Desipramine appears to be somewhat more likely than other TCAs to lead to death in overdose. Amitriptyline, clomipramine, dothiepin/dosulepin, doxepin, trimipramine and imipramine showed broadly similar toxicity and were usually reported to be less toxic than desipramine. Data on nortriptyline were contradictory. Lofepramine had the lowest risk of death in overdose. The rank order of overdose toxicity was broadly consistent between different FTI definitions and between markers used. With respect to the risk of cardiovascular events at clinically relevant exposure, amitriptyline, nortriptyline and lofepramine were associated with a greater risk of in-use cardiotoxicity. All measures of overdose toxicity were subject to external influences and confounding. The continued use of TCAs in depression and other conditions should be minimized when considering their undoubted toxicity in overdose and possible toxicity in normal clinical use.