Treatment of acute mania has been greatly influenced by loading strategies. Loading has potential benefits, including rapid symptom reduction in mania and a shortened length of stay. Disadvantages include an increased likelihood of adverse effects of the medications. Loading strategies for lithium, valproic acid (divalproex sodium), carbamazepine, oxcarbazepine, olanzapine, and haloperidol decanoate in the treatment of acute mania are discussed. Recent studies highlight this treatment option for selected patients. It is the unique properties of the medications that influence their use in loading. Issues in patient selection for loading strategies with each medication are also considered.
Background
Pharmacodynamics and pharmacogenetics are being explored in pharmacological treatment response for major depressive disorder (MDD). Interactions between genotype and treatment response may be dose dependent. In this study, we examined whether MDD patients with
Met/Met, Met/Val, and Val/Val COMT
genotypes differed in their response to bupropion in terms of depression scores.
Methods
This study utilized a convenience sample of 241 adult outpatients (≥18 years) who met DSM‐5 criteria for MDD and had visits at a Midwest psychopharmacology clinic between February 2016 and January 2017. Exclusion criteria included various comorbid medical, neurological, and psychiatric conditions and current use of benzodiazepines or narcotics. Participants completed genetic testing and the 9 question patient‐rated Patient Health Questionnaire (PHQ‐9) at each clinic visit (
M
= 3.8 visits,
SD
= 1.5) and were prescribed bupropion or another antidepressant drug. All participants were adherent to pharmacotherapy treatment recommendations for >2 months following genetic testing.
Results
Participants were mostly Caucasian (85.9%) outpatients (154 female and 87 male) who were 44.5 years old, on average (
SD
= 17.9). For
Val
carriers, high bupropion doses resulted in significantly lower PHQ‐9 scores than no bupropion (
t
(868) = 5.04,
p
< .001) or low dose bupropion (
t
(868) = 3.29,
p
= .001).
Val
carriers differed significantly from
Met/Met
patients in response to high dose bupropion (
t
(868) = −2.03,
p
= .04), but not to low dose bupropion.
Conclusion
High‐dose bupropion is beneficial for MDD patients with
Met/Val
or
Val/Val COMT
genotypes, but not for patients with
Met/Met
genotype. Prospective studies are necessary to replicate this pharmacodynamic relationship between bupropion and
COMT
genotypes and explore economic and clinical outcomes.
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