_______________________________________________________________________ Depression and Suicide
and MAOIs. Selection of a second-generation antidepressant is often recommended for initial treatment due to quality of published data, side effect profile compared to TCAs and MAOIs, and relative safety [21; 22; 156]. The choice of medica- tion should be based on the following considerations: patient preference; nature of prior patient or family member response to medication; safety, tolerability, and anticipated side effects; co-occurring conditions and potential drug-drug interactions; cost [21; 22]. For most patients, a SSRI, a SNRI, mirtazapine, or bupropion is optimal for initial therapy. The use of MAIOs should be restricted to patients who do not respond to other treatments [21; 22]. The three most distressing side effects for patients treated with antidepressants are sleep disturbance, sexual dysfunction, and weight gain [157]. Choice of medication should be guided by knowledge of comparative side effects and patient priorities;
some patients will be more concerned about sexual side effects, while for others, nausea, sleep disturbances, or weight gain may be more distressing [64]. In addition, available evidence regarding the optimal pharmacotherapeutic selection for the treatment of dimensions of depression and DSM-5-TR speci- fiers should be considered ( Table 1 ). Selective Serotonin Reuptake Inhibitors SSRIs are thought to act by inhibiting serotonin transporters (SERT) that reuptake serotonin (5-HT) into the presynap- tic cell, increasing 5-HT in the synaptic cleft. SSRIs have advantages of low overdose lethality and better tolerability than first-generation antidepressants, which can improve adherence. SSRIs are particularly effective in patients with obsessive-compulsive symptoms but may initially worsen anxiety or panic symptoms [21; 22; 122]. This class includes
RECOMMENDATIONS FOR MDD SPECIFIERS AND DIMENSIONS
Specifier or Dimension
Recommended Agent(s)
Anxious distress
Antidepressants with efficacy in generalized anxiety disorder (SSRIs, SNRIs, and bupropion comparable in efficacy)
Mixed features
Lurasidone Asenapine Quetiapine Aripiprazole Ziprasidone
Melancholic features
TCAs SNRIs
Atypical features Psychotic features Catatonic features Seasonal pattern
MAOIs (superior to TCAs in older studies) Antipsychotic-antidepressant combinations
Benzodiazepines SSRIs Agomelatine Bupropion Moclobemide
Cognitive dysfunction a
Vortioxetine (highest efficacy) Bupropion Duloxetine Modafinil Moclobemide
Sleep disturbance a
Agomelatine (highest efficacy) Mirtazapine Quetiapine Trazodone (high rates of somnolence and daytime sedation)
Fatigue a
Bupropion (highest efficacy) SSRIs
Low energy a
Duloxetine
Neuropathic pain and fibromyalgia a
Duloxetine (highest efficacy) Amitriptyline Other SNRIs
a Clinical dimension not recognized in the DSM-5-TR. Source: [158; 159; 160]
Table 1
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