The Mood Map

Best safety profile, most evidence, well tolerated. Takes 4-6 weeks for full effect. If no response at adequate dose for 6-8 weeks, switch to a different SSRI or augment.

FDA-approved for MDD, GAD, diabetic neuropathy, fibromyalgia, and chronic musculoskeletal pain. The NE component provides descending pain inhibition. Two birds, one drug.

Bupropion (NDRI) has no serotonergic activity → no sexual side effects. Can also be added to an SSRI as augmentation. Alternative: mirtazapine (lower rate of sexual dysfunction).

The only antidepressant that doubles as a smoking cessation aid. Blocks NE and dopamine reuptake, reducing cravings and withdrawal. Check for seizure risk factors first.

Side effects = treatment: sedation helps sleep, appetite stimulation helps weight. H1 and 5-HT2C blockade. No anticholinergic effects (safe in elderly unlike TCAs).

Options: (1) Add lithium or atypical antipsychotic (aripiprazole, quetiapine) to current SSRI. (2) Switch to MAOI after 2-week washout. (3) Ketamine/esketamine (Spravato) · rapid acting, works within hours. MAOIs are last resort.

Sertraline has the most reassuring pregnancy data. Fluoxetine also commonly used. Avoid paroxetine (cardiac defects). Do NOT stop antidepressants without replacement · untreated maternal depression harms the fetus.

Best safety profile, most evidence, well tolerated. Start low, titrate over 2-4 weeks, allow 6-8 weeks at therapeutic dose before declaring failure. Escitalopram has fewest drug interactions. Sertraline has the best pregnancy data if reproductive age.

Citalopram and escitalopram have dose-dependent QT prolongation. For patients with known QT concern, choose sertraline (lowest QT risk among SSRIs) or bupropion (NDRI, no serotonin, no QT effect). Bupropion is also suitable if stimulating properties are beneficial.

Bupropion has no serotonergic activity, so no sexual side effects. Works on NE and dopamine instead. Can also be added to the SSRI as augmentation rather than a full switch if the SSRI is working well. Contraindicated in eating disorders (seizure threshold) and active alcohol withdrawal.

Bupropion (NDRI): lowest sexual side effect rate of any antidepressant. Good if the patient also has fatigue or cognitive slowing. Mirtazapine: low sexual dysfunction rate but causes weight gain and sedation (therapeutic in some, problematic in others). Avoid SSRIs/SNRIs if sexual function is a primary concern from the start.

Bupropion is the only antidepressant FDA-approved for smoking cessation. NDRI mechanism reduces cravings by affecting dopamine and NE pathways. Screen for seizure history (absolute contraindication), active eating disorder, and alcohol use disorder before starting.

Mirtazapine causes weight gain (H1 blockade) and sedation (antihistamine effect). In this elderly patient those are the goals. It also blocks 5-HT2C and alpha-2 receptors. Avoid TCAs in the elderly (anticholinergic: urinary retention, confusion, falls, QT prolongation). Mirtazapine has no anticholinergic activity.

Duloxetine is FDA-approved for MDD, GAD, diabetic neuropathy, fibromyalgia, and chronic musculoskeletal pain. The norepinephrine component activates descending pain inhibition pathways. Milnacipran is an SNRI approved specifically for fibromyalgia if depression is the secondary concern.

Sertraline has the most reassuring data for use in pregnancy. Fluoxetine is also commonly used. Avoid paroxetine (associated with cardiac septal defects in first trimester). Do NOT stop antidepressants without a replacement plan: untreated maternal depression causes preterm birth and developmental issues. The risk of untreated illness outweighs medication risk for most patients.

SSRIs (sertraline, escitalopram) and SNRIs (venlafaxine, duloxetine) are first-line for panic disorder with comorbid depression. Key: START at a very low dose. SSRIs can paradoxically worsen anxiety in the first 1-2 weeks (activating effect). Titrate slowly. Add a short-term benzodiazepine for bridging if the activation is severe.

For MDD plus GAD: duloxetine (FDA-approved for both MDD and GAD) or escitalopram (fewest drug interactions, FDA-approved for GAD). Buspirone can be added for GAD augmentation but does not treat depression. Avoid benzodiazepines as long-term monotherapy in GAD: they cause dependence and do not treat the underlying depression.

Historically MAOIs were considered superior for atypical features. On boards, SSRIs are still first-line. MAOIs (phenelzine, tranylcypromine) are reserved for treatment-resistant atypical depression after failing SSRIs and SNRIs. The reason: dietary restrictions (tyramine) and drug interactions make MAOIs too dangerous for first use.

After 2+ SSRI failures in atypical MDD, MAOIs are the historical gold standard. Require a 2-week washout after stopping an SSRI (5 weeks for fluoxetine). Strict tyramine diet: no aged cheese, cured meats, red wine, soy. Avoid tramadol, meperidine, triptans, dextromethorphan (serotonin syndrome risk). Not first-line, but they work.

MDD with psychotic features requires BOTH an antidepressant AND an antipsychotic. Antidepressant alone will not clear the delusions. Antipsychotic alone will not resolve the mood. After remission, the antipsychotic is typically tapered (unlike schizophrenia). ECT is highly effective for psychotic depression and may be considered upfront in severe cases.

In bipolar depression, antidepressant monotherapy can trigger a manic switch. First-line options: quetiapine, lurasidone (with food), or olanzapine-fluoxetine combination (OFC). Lithium and lamotrigine are mood stabilizers with antidepressant properties in bipolar. If an antidepressant is added, always pair it with a mood stabilizer or atypical antipsychotic as a cover.