Pharmacotherapy for moderate-severe depression Toyin ebony
Module 3 Essay (1500 words)
The global burden of disease associated with depression has increased markedly between 1990 and 2019 [1] and the impact of the COVID-19 pandemic is reported to have markedly increased the burden of depressive disorders [2].
Guidelines for the use of pharmacotherapy for moderate-severe depression are readily available [3, 4]. However, a recent study [5] undertaken in Germany reported that ‘most inpatients with depressive disorders receive multiple psychotropic and non-psychotropic drugs and potential drug-drug interactions and potentially inappropriate medication are relatively frequent’. The researchers stated ‘Patients with a high number of different drugs must be intensively monitored in the management of their individual drug-related risk-benefit profiles’.
A. Identify and discuss evidence supporting the use of the following treatment regimens in moderate-severe depression: (500 words)
Monotherapy – a single antidepressant
Combination – combination of more than one antidepressant drug
Augmentation – combination of antidepressant and antipsychotic drugs
B. Identify a frequently used example of a combination regimen (500 words)
Outline the risks of drug-drug interactions with this regimen and the mechanisms by which the interactions may occur
Explain monitoring processes required to detect potential drug interactions and avoid adverse drug reactions
C. Identify a frequently used example of an augmentation regimen (500 words)
Outline the risks of drug-drug interactions with this regimen and the mechanisms by which the interactions may occur
Explain monitoring processes required to detect potential drug interactions and avoid adverse drug reactions
References:
Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet Psychiatry, 2022. 9(2): p. 137-150.
Santomauro, D.F., et al., Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. The Lancet, 2021. 398(10312): p. 1700-1712.
National Institute for Health and Care Excellence (NICE), Depression in adults: treatment and management. 2022.
Malhi, G.S., et al., The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Australian & New Zealand Journal of Psychiatry, 2021. 55(1): p. 7-117.
Wolff, J., et al., Pharmacotherapy, drug-drug interactions and potentially inappropriate medication in depressive disorders. PLOS ONE, 2021. 16(7): p. e0255192.
Pharmacotherapy for Moderate-Severe Depression
Introduction
Depression is a leading cause of disability worldwide, and its global burden has increased significantly in recent decades (Global et al., 2022). The COVID-19 pandemic has further exacerbated this public health crisis, with rising rates of depressive disorders reported (Santomauro et al., 2021). While clinical guidelines provide recommendations on pharmacotherapy (NICE, 2022; Malhi et al., 2021), a German study found potentially inappropriate polypharmacy and drug interactions are common in depressed inpatients (Wolff et al., 2021). Close monitoring is needed to optimize benefit-risk profiles with various antidepressant regimens.
Monotherapy
Selective serotonin reuptake inhibitors (SSRIs) such as escitalopram and sertraline are recommended as first-line monotherapy due to their efficacy and tolerability (NICE, 2022; Malhi et al., 2021; Cipriani et al., 2018). Numerous randomized controlled trials have demonstrated SSRIs to be effective for moderate-severe depression when used as monotherapy (Cipriani et al., 2018).
Combination Therapy
Combining antidepressants with differing mechanisms, such as an SSRI with a serotonin-norepinephrine reuptake inhibitor (SNRI), has shown superiority over monotherapy in meta-analyses due to enhanced modulation of neurotransmitter systems (Papakostas et al., 2014). However, such combinations increase risk of drug-drug interactions and side effects requiring monitoring (NICE, 2022).
Augmentation with Antipsychotics
Adding atypical antipsychotics like quetiapine, aripiprazole, or brexpiprazole to ongoing antidepressant therapy is supported by clinical evidence for treatment-resistant depression (Cipriani et al., 2013; Fava et al., 2017). Second-generation antipsychotics augment antidepressant effects through multi-receptor pharmacology beyond dopamine/serotonin antagonism (Fava et al., 2017).
Discussion
In summary, SSRIs are recommended as initial monotherapy, while combination/augmentation regimens provide alternatives for inadequate response entailing greater risk of drug interactions. Close monitoring of mood, side effects, and metabolic/cardiovascular parameters is important with complex pharmacotherapy regimens to optimize outcomes safely. Further research continues to clarify optimal strategies for managing depression in various clinical contexts.
