Backing into the future: pharmacological approaches to the management of resistant depression

Abstract

Pragmatic studies indicate that a substantial number of depressed patients do not remit with current first-line antidepressant treatments and after two failed treatment steps the chance of remission with subsequent therapies is around 15%. This paper focuses on current evidence for pharmacological treatments in resistant depression as well as possible future developments. For patients who have failed to respond to two antidepressant trials, augmentation with atypical antipsychotic drugs, specifically quetiapine and aripiprazole, has the best evidence for efficacy, though older treatments such as lithium and triiodothyronine still have utility. The striking antidepressant effect of ketamine in resistant depression has stimulated research into glutamatergic compounds; however, capturing the efficacy of ketamine with drugs suitable for continuous use has proved challenging. Growing knowledge of the pathophysiological role of inflammation in depression offers great opportunities for future treatment in terms of repurposing anti-inflammatory agents from general medicine and pre-treatment stratification of those depressed patients in whom such interventions are likely to be beneficial. Finally an older drug, the dopamine receptor agonist pramipexole, if used carefully may well improve the prospects of depressed patients who are refractory to current approaches.

Pramipexole in the treatment of unipolar and bipolar depression. A systematic review and meta‐analysis

“…Indeed, in observational studies pramipexole was prescribed at flexible and higher doses than in RCTs . These results are supported by other authors , who underscored the importance of adequate dosage for pramipexole to exert its full effect. Observational studies reported higher response and remission rates than RCTs also for traditional antidepressants .…”

“…In the last 15 years, substantial efforts have been made to evaluate the efficacy and the safety of pramipexole for the treatment unipolar and bipolar depression, both in monotherapy and as adjunctive treatment. The available reviews focused on a limited number of trials , or on randomized controlled trials (RCTs) , or on trials including only patients with bipolar depression .…”

Effect of Physical State on Pain Mediated Through Emotional Health in Rheumatoid Arthritis

“…Evidence shows that the physical state affects emotional health . Several hypotheses concerning the mechanisms whereby inflammation potentially influences emotional health have been put forward, including dysregulation of the hypothalamic pituitary adrenal axis, changes in glial function and glutamate release in the brain, and activation of the tryptophan metabolizing enzyme . Of particular interest are findings of clinical studies showing that antiinflammatory drugs are effective in treating patients with depression .…”

Aripiprazole as a mood stabiliser in postpartum depression with premorbid passive-dependent personality structure: A case report

“…to the United States Food and Drug Administration (FDA) received approval for use in addition to antidepressants in the treatment of a severe depressive episode. [11][12][13][14] In this case, it was shown that the combination of antidepressants with aripiprazole led to the withdrawal of the symptoms of depression, with long-term persistence and without the occurrence of subsequent sudden mood disorders. Bearing in mind the long history of use of antidepressants and psychotherapy combined, which gave no desired results, it was concluded that adding of aripiprazole as an additional therapy proved to be extremely useful.…”