A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine.

OBJECTIVE: To determine the relative cost-effectiveness of three classes of antidepressants: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and the modified TCA lofepramine, as first choice treatments for depression in primary care. DESIGN: Open, pragmatic, controlled trial with three randomised arms and one preference arm. Patients were followed up for 12 months. SETTING: UK primary care: 73 practices in urban and rural areas in England. PARTICIPANTS: Patients with a new episode of depressive illness according to GP diagnosis. INTERVENTIONS: Patients were randomised to receive a TCA (amitriptyline, dothiepin or imipramine), an SSRI (fluoxetine, sertraline or paroxetine) or lofepramine. Patients or GPs were able to choose an alternative treatment if preferred. MAIN OUTCOME MEASURES: At baseline the Clinical Interview Schedule, Revised (CIS-R PROQSY computerised version) was administered to establish symptom profiles. Outcome measures over the 12-month follow-up included the Hospital Anxiety and Depression Scale self-rating of depression (HAD-D), CIS-R, EuroQol (EQ-5D) for quality of life, Short Form (SF-36) for generic health status, and patient and practice records of use of health and social services. The primary effectiveness outcome was the number of depression-free weeks (HAD-D less than 8, with interpolation of intervening values) and the primary cost outcome total direct NHS costs. Quality-adjusted life-years (QALYs) were used as the outcome measure in a secondary analysis. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were computed. Estimates were bootstrapped with 5000 replications. RESULTS: In total, 327 patients were randomised. Follow-up rates were 68% at 3 months and 52% at 1 year. Linear regression analysis revealed no significant differences between groups in number of depression-free weeks when adjusted for baseline HAD-D. A higher proportion of patients randomised to TCAs entered the preference arm than those allocated to the other choices. Switching to another class of antidepressant in the first few weeks of treatment occurred significantly more often in the lofepramine arm and less in the preference arm. There were no significant differences between arms in mean cost per depression-free week. For values placed on an additional QALY of over 5000 pounds, treatment with SSRIs was likely to be the most cost-effective strategy. TCAs were the least likely to be cost-effective as first choice of antidepressant for most values of a depression-free week or QALY respectively, but these differences were relatively modest. CONCLUSIONS: When comparing the different treatment options, no significant differences were found in outcomes or costs within the sample, but when outcomes and costs were analysed together, the resulting cost-effectiveness acceptability curves suggested that SSRIs were likely to be the most cost-effective option, although the probability of this did not rise above 0.6. Choosing lofepramine is likely to lead to a greater proportion of patients switching treatment in the first few weeks. Further research is still needed on the management of depressive illness in primary care. This should address areas such as the optimum severity threshold at which medication should be used; the feasibility and effectiveness of adopting structured depression management programmes in the UK context; the importance of factors such as physical co-morbidity and recent life events in GPs' prescribing decisions; alternative ways of collecting data; and the factors that give rise to many patients being reluctant to accept medication and discontinue treatment early.

Assessing the effect of patient and prescriber preference in trials of treatment of depression in general practice.

Preferences include the choices made by individuals when presented with options for treatment for depression, and the system of beliefs and views that underlies those choices. They are informed by the experience of previous treatment by individuals, their family and friends, information from medical professionals and the media, and incorporates biases and ideologies present within the population. Although the randomised controlled trial is generally considered to be the optimal method for evaluating the effectiveness of health care interventions, [1] patients may become less motivated to follow the treatment protocol if they are not allocated to their preferred treatment. Consequently, the relevant arms of the study may appear less effective as a result. Further, following an invitation to join a clinical trial, patients may refuse randomisation and be excluded from the trial if they have strong treatment preferences, leading to the introduction of bias and restricted ability to generalise the results, as participants may not be representative. Considerable demand has been shown by patients for psychological treatments for the treatment of depression in primary care. However, two recent studies have not demonstrated a relationship between being allowed to choose treatment and short-term depression outcome. These two studies explored primary care patients treated with antidepressants or counselling, and non-directive counselling, cognitive-behaviour therapy or usual general practitioner care. Further work is needed to determine the effects of preferences within different study designs and to explore the views of both professionals and patients using appropriate qualitative designs.

Cell and matrix biology of the suprapatella in the rat: a structural and immunocytochemical study of fibrocartilage in a tendon subject to compression.

The structure, ultrastructure, histochemistry, and immunohistochemistry of the suprapatella have been described in the rat. The suprapatella is a fibrocartilaginous sesamoid within the tendon of quadriceps femoris that articulates with the femoral condyles during flexion of the knee joint and reduces the amount of bending required at the tendon-bone junction. The cells of the suprapatella were much larger and more numerous than those in the associated tendon and were packed with vimentin-containing, intermediate filaments. The tendon cells contained far fewer filaments. The cells of both regions contained actin and tubulin. Histochemical and immunohistochemical studies showed that the suprapatellar cells were embedded in a matrix that is rich in chondroitin sulphate, but does not contain keratan or heparan sulphate. The fibrocartilage of the adjacent attachment zone of the quadriceps tendon also contained chondroitin sulphate, but in addition was rich in type II collagen. The structure of the suprapatella was similar to that of the fibrocartilaginous regions of tendons that pass around bony pulleys. However, there were differences in matrix composition that could reflect functional differences between the fibrocartilages.