Abstract
BackgroundTraditionally tricyclic antidepressants (TCAs) have an important place in treatment of major depressive disorder (MDD). Today, often other antidepressant medications are considered as first step in the pharmacological treatment of MDD, mainly because they are associated with less adverse effects, whereby the position of TCAs appears unclear. In this study we aimed to examine the current practice of TCAs in treatment of unipolar MDD.MethodsA mixed methods approach was applied. First, a selection of leading international and national guidelines was reviewed. Second, actual TCA prescription was examined by analyzing health records of 75 MDD patients treated with the TCAs nortriptyline, clomipramine or imipramine in different centers in the Netherlands. Third, promotors and barriers influencing the choice for TCAs and dosing strategies were explored using semi-structured interviews with 24 Dutch psychiatrists.ResultsClinical practice guidelines were sometimes indirective and inconsistent with each other. Health records revealed that most patients (71%) attained therapeutic plasma concentrations within two months of TCA use. Patients who achieved therapeutic plasma concentrations reached them on average after 19.6 days (SD 10.9). Both health records and interviews indicated that therapeutic nortriptyline concentrations were attained faster compared to other TCAs. Various factors were identified influencing the choice for TCAs and dosing by psychiatrists.ConclusionsGuideline recommendations and clinical practice regarding TCA prescription for MDD vary. To increase consistency in clinical practice we recommend development of an up-to-date guideline integrating selection and dosing of TCAs, including the roles of therapeutic drug monitoring and pharmacogenetics. Such a guideline is currently lacking and would contribute to optimal TCA treatment, whereby efficacy and tolerability may be increased.
Highlights
Major depressive disorder (MDD) is among the leading causes of disability worldwide with a lifetime risk of 15 to 18% and over 264 million people affected globally [1, 2]
They agree that Tricyclic antidepressant (TCA) are associated with more adverse effects and that they are more dangerous in overdose
Guidelines by the World Health Organization (WHO), World Federation of Societies of Biological Psychiatry (WFSBP), Deutsche Gesellschaft für Psychiatrie, Psychotherapie und Nervenheilkunde (DGPPN) and the Dutch guideline state no general preference between TCAs, Selective serotonin reuptake inhibitor (SSRI), Serotonin-noradrenaline reuptake inhibitor (SNRI) and the other modern antidepressants mirtazapine and bupropion, except for subgroups of patients [10, 13, 16,17,18]
Summary
Major depressive disorder (MDD) is among the leading causes of disability worldwide with a lifetime risk of 15 to 18% and over 264 million people affected globally [1, 2]. Over the last decades, SSRIs, SNRIs and other modern antidepressants are increasingly considered as first-line agents, mainly because they are associated with less adverse effects and since they are less dangerous in overdose [3,4,5,6]. TCAs continue to be prescribed, if only because of the common occurrence of non-response to SSRIs and SNRIs, but the current position of TCAs in pharmacotherapy of unipolar MDD is unclear [3, 4]. An advantage of TCAs over SSRIs and SNRIs is that therapeutic plasma concentrations associated with optimal efficacy are defined [7]. Tricyclic antidepressants (TCAs) have an important place in treatment of major depressive disorder (MDD). Often other antidepressant medications are considered as first step in the pharmacological treatment of MDD, mainly because they are associated with less adverse effects, whereby the position of TCAs appears unclear.
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