Weatherly's Woes - Depression

MAJOR DEPRESSIVE DISORDER

The big sad

Major Depressive Disorder (MDD) is the infamous “depression.”

What are the DSM diagnostic criteria?

You have to meet 5 of the 9 depression criteria for 2 weeks straight. The classic mnemonic for remembering the criteria is “SIG E CAPS.” I don’t like it. How is that easy to remember? Wtf is a SIG? Also, SIG E CAPS omits the letter “D.” So I made up a new acronym -- SPICED GAS. (When you eat an entire bag of Takis, the next morning you’ll be really depressed when you wake up with burning gastrointestinal distress…. hence SPICED GAS). ***Of the 5 criteria, one of them must be D or I.

SPICED GAS

Sleep loss

Psychomotor stuff

Interest loss (anhedonia)***

Concentration decreases (brain fog)

Energy loss (fatigue)

Depression***

Guilt

Appetite loss

Suicidal ideations

What are the different MDD modifiers?

Depression has a few different spin-off flavors. There is MDD with anxious features, with melancholic features (extra sad) or with atypical features (they gain weight and sleep more).

What exactly is atypical depression?

I don’t have a great understanding of the pathophysiology of this one, so I’m just going to mention the criteria. You have to meet 2+ of the 4 criteria: eating MORE, sleeping MORE, the sensation of heaviness in your limbs and feeling very sensitive to criticism from other folks. It’s good to know that atypical depression responds really well to MAO Inhibitors, although this dangerous medication is still 2nd line to SSRIs and SNRIs.

Treatment?

In general, drugs affecting serotonin help with depression and anxiety. Drugs affecting norepinephrine help with depression and chronic pain. In recent decades, SSRIs, SNRIs and NDRI antidepressants have replaced TCAs and MAOIs as first-line drugs due to their great side-effect profile and safety in the event of an acute overdose (it’s nearly impossible to OD on SSRIs). Antidepressants take several weeks to start working, but don’t take full effect for 4-6 weeks.

PERSISTENT DEPRESSIVE DISORDER

Dysthymia

Persistent Depressive Disorder is mild depression over a long period of time. It used to be called “dysthymic disorder.”

How is it different from Major Depressive Disorder?

MDD requires 5 / 9 criteria for 2 weeks.

PDD requires 3 / 9 criteria for 2 years. PDD patients are often much higher functioning, usually able to hold down a job and family. They’re just not that happy. Their symptoms are mild enough that they often don’t seek treatment for years and years.

Treatment?

Low doses of SSRIs or SNRIs.

THE PSYCH TIMELINE

The Timeline is important when making a diagnosis in Psych.

Some disorders can ONLY be distinguished by the timeline, and they make for great test questions!

DEPRESSION DRUGS

GOLD STANDARD

SSRIs and SNRIs are the first and second-line drugs for depression and anxiety. And if the first drug doesn’t work, do a trial of a different one! These are some of the most commonly prescribed drugs in the US.

SSRIs - overall a very safe class, low toxicity in an overdose, also treats anxiety, lots of sexual side effects (For sexual side effects that are particularly bad, add Bupropion, Mirtazapine or Viagra if the SSRI/SNRI is working really well. If it isn’t working, then taper down the SSRI/SNRI and switch to Escitalopram). All SSRIs have a black box warning for increased suicidality in those under 25 (update - recent evidence suggests this is wrong). When you withdraw from SSRIs, you get the FINISH syndrome (Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory weirdness, Hyperarousal). To avoid FINISH, slowly taper off.

- Fluoxetine - safe in kids, longest half-life (14 d), treats eating disorders, 2D6 Inhibitor

- Sertraline - treats PTSD

- Citalopram - most QT prolongation

- Escitalopram - fewest sexual side effects

- Paroxetine - dirty drug, shortest half-life (FINISH withdrawal symptoms), teratogen, 2D6 Inhibitor, anticholin

- Fluvoxamine - only for OCD

SNRIs (Venlafaxine, Duloxetine) - at a low dose they’re SSRIs. At higher doses they affect Norepi, hence there is a dose-dependent increase in diastolic BP. At very extreme doses it affects Dopamine and can cause EPS. But mostly very similar to SSRIs, with the added benefit of treating chronic pain

SILVER STANDARD

SSRIs and SNRIS should be your usual first choice, but it’s okay to use these right off the bat in the right patient.

Serotonin Modulators - at lower doses they mostly affect histamine/α, so it’s safe to stack on an SSRI/SNRI

- Trazodone - 5HT2-Blocker, side effects (priapism / sedation / orthostatic hypotension), helpful for falling asleep

Atypicals - frequently stacked on top of SSRIs / SNRIs due to their negligible risk of Serotonin Syndrome

- Bupropion - NDRI, improves sex, brightens affect, stimulant-like, ↑seizures, don’t give if electrolytes bad/anorexic, ↓smoking cravings!

- Mirtazapine - α2-Blocker / 5-HT2-Blocker / 5-HT3-Blocker / H1-Blocker, fat and sleepy (weight gain, fatigue)

Quetiapine / Aripiprazole - these antipsychotics are approved for complicated, or treatment resistant cases.

BRONZE STANDARD

Try to avoid these if you can. But depression is hard to treat, so lots of people end up on TCAs. NEVER start someone on an MAOI, the side effects are far too toxic -- only psychiatrists should be prescribing this class.

TCAs - similar MOA to SNRIs, anticholinergic, very deadly in an overdose because 7 days of pills can cause the 3 killer C’s (cardiotoxic, coma, convulsions), antidote is sodium bicarbonate.

- Amitriptyline - chronic pain, migraines, anticholinergic

- Clomipramine - OCD, less anticholinergic → safer in elderly

- Desipramine - chronic pain

MAOIs (Phenelzine, Selegiline, Isocarboxazid) - very effective but very dangerous, 2nd line for atypical MDD, eating tyramine-containing foods (aged meats/cheese/wine) precipitates a hypertensive crisis

Serotonin Syndrome - sympathetic (high vital signs) & neuromuscular (hyperreflexia) overload caused by combining multiple serotonergic agents (SS/NRIs, MAOIs, TCAs, triptans, trazodone). Stop drugs if occurs, though can be prevented (don’t combine too many serotonergic agents!). Symptoms include rapid onset agitation and ramped up vitals. Non-serotonergic alternatives: mirtazapine and bupropion (minimally serotonergic). See dedicated page.