Differential Treatment Effectiveness in Patients with the melancholic sub-type of depression

There are three treatment groups in this trial. Current routine management for patients who present with melancholic depression include prescribing citalopram (SSRI) or referral to undergo cognitive behavioural therapy. This study will compare these two management options with a treatment developed through clinical experience, the Sequencing Drug-based Algorithm. Sequencing Drug-based Algorithm (SDA): Those receiving the SDA protocol will initially receive the dual action antidepressant drug venlafaxine (i.e. impacting on serotonergic and noradrenergic functioning), initially daily at 75 mg and progressively titrated up to maximum dose of 300 mg over three weeks – subject to side-effects and response. If no ‘response’ (operationalised as 50% or more improvement in Hamilton score), augmentation by the low dose atypical antipsychotic olanzapine (i.e. 2.5 mg daily) will be initiated in the fourth week, with the latter ceased (at the end of the fifth week) if the subject’s depression remits and the dual action antidepressant maintained. If no ‘response’ or, if a recurrence after ceasing the augmenting drug, the venlafaxine drug will be tapered and ceased over two weeks, and the tricyclic antidepressant drug nortriptyline introduced in the eighth week will be taken daily, and again augmented with an atypical antipsychotic drug if no formal ‘response’ after two weeks for a maximum of two weeks while the tricyclic will be maintained until the end of the twelfth week. [Nortriptyline is chosen as the tricyclic drug, as it has been the most common tricyclic comparator compared to cognitive behaviour therapy]. Each participant will attend eight, 30 minute consultations over the twelve week treatment intervention period.