Psychiatry - Research Publications

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    Chronic adrenocorticotrophic hormone treatment alters tricyclic antidepressant efficacy and prefrontal monoamine tissue levels
    Walker, AJ ; Burnett, SA ; Hasebe, K ; McGillivray, JA ; Gray, LJ ; McGee, SL ; Walder, K ; Berk, M ; Tye, SJ (ELSEVIER, 2013-04-01)
    Several animal models are currently utilised in the investigation of major depressive disorder; however, each is validated by its response to antidepressant pharmacotherapy. Few animal models consider the notion of antidepressant treatment resistance. Chronic daily administration of adrenocorticotropic hormone (ACTH) or corticosterone can alter behavioural responses to antidepressants, effectively blocking antidepressant efficacy. Herein, we demonstrate that ACTH-(1-24) (100μg/day; 14 days) blocks the immobility-reducing 'antidepressant' effects of a single dose of imipramine (10mg/kg) in the forced swim test. This finding was accompanied by altered monoamine tissue levels in the prefrontal cortex (PFC) 1h after exposure to the acute stress of the forced swim test. PFC tissue from ACTH pre-treated animals contained significantly higher serotonin, noradrenaline and adrenaline concentrations relative to saline pre-treated controls. Conversely, dopamine levels were significantly decreased. Altered plasma corticosterone responses to ACTH injections were observed over the treatment course. Measures were taken on treatment days 1, 4, 8, 11, 14 and 15. ACTH administration initially enhanced plasma corticosterone levels, however, these normalised to levels consistent with control animals by day 14. No differences in corticosterone levels were observed across the treatment time course in saline-treated animals. Taken together these results indicate that pre-treatment with ACTH (100μg/day; 14 days) blocks the antidepressant effects of imipramine (10mg/kg), significantly alters key PFC monoamine responses to stress and downregulates glucocorticoid responses. These results suggest that chronic ACTH treatment is a promising paradigm for elucidation of mechanisms mediating antidepressant treatment resistance.
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    Pharmacological management of unipolar depression
    Malhi, GS ; Hitching, R ; Berk, M ; Boyce, P ; Porter, R ; Fritz, K (WILEY, 2013-05)
    Objective To be used in conjunction with ‘Psychological management of unipolar depression’ [Lampe et al. Acta Psychiatr Scand 2013;127(Suppl. 443):24–37] and ‘Lifestyle management of unipolar depression’ [Berk et al. Acta Psychiatr Scand 2013;127(Suppl. 443):38–54]. To provide clinically relevant recommendations for the use of pharmacological treatments in depression derived from a literature review. Method Using our previous Clinical Practice Guidelines [Malhi et al. Clinical practice recommendations for bipolar disorder. Acta Psychiatr Scand 2009;119(Suppl. 439):27–46] as a foundation, these clinician guidelines target key practical considerations when prescribing pharmacotherapy. A comprehensive review of the literature was conducted using electronic database searches (PubMed, MEDLINE), and the findings have been synthesized and integrated alongside clinical experience. Results The pharmacotherapy of depression is an iterative process that often results in partial and non‐response. Beyond the initiation of antidepressants, the options within widely used strategies, such as combining agents and switching between agents, are difficult to proscribe because of the paucity of pertinent research. However, there is some evidence for second‐line strategies, and a non‐prescriptive algorithm can be derived that is based broadly on principles rather than specific steps. Conclusion Depression is by its very nature a heterogeneous illness that is consequently difficult to treat. Invariably, situation‐specific factors often play a significant role and must be considered, especially in the case of partial and non‐response. Consulting with colleagues and trialling alternate treatment paradigms are essential strategies in the management of depression.