Antidepressants

General information

Antidepressants are drugs used for the treatment of major depressive disorder and other conditions, such as anxiety disorders, OCD, and various neurological disorders. To establish efficacy, an antidepressant must show that it can produce a therapeutic effect for the condition for which it is taken. An antidepressant should be determined to be more efficacious than placebo to justify the risk associated with side effects.

Common Antidepressants

SSRIs

These drugs inhibit the reuptake of serotonin. This increases the amount of extra cellular serotonin leading to a larger response on 5-HT receptors.

Citalopram (Celexa)

Fluoxetine (Prozac)

Sertraline (Zoloft)

Escitalopram (Lexapro)

Paroxetine (Paxil)

SNRIs

These drugs inhibit the reuptake of both serotonin and norepinephrine.

Desvenlafaxine (Pristiq)

Duloxetine (Cymbalta)

Venlafaxine (Effexor)

SARIs

These act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine.

Etoperidone (Axiomin, Centren, Depracer, Etonin, Etoran, Staff, Tropene)

Nefazodone (Dutonin, Nefadar, Serzone)

Trazodone (Desyrel)

NDRIs

Inhibits the reuptake of norepinephrine and dopamine.

Bupropion (Wellbutrin)

MAOIs

Inhibit monoamine oxidase, a chemical in the brain and stomach that breaks down monoamines. Monoamine is a chemical used in cellular respiration to seperate an amine group of a molecule to allow easier uptake.

There are many types of MAOIs, reversable indicates monoamine oxidase is inhibited for a brief time, irreversable MAOIs typically inhibit monoamine oxidase for about 2 weeks.

Selective MAOIs only inhibit either MAOI-A or MAO-B (See note for MAO-B selective inhibation below) these are considered "safer" than nonselective MAOIs as small amounts of tyranmine can still be processed, avoiding the "Cheese Effect" commonly associated with consumption of tyranmine rich foods while monoamine oxidase is inhibitted.

Selective
- MAO-A
  - Natural
    - Harmala and harmala alkaloids.
    - Peganum Harmala (Syrian Rue)
    - Harmine
    - Harmalol
    - Piperine
  - Synthetic
    - Brofaromine (Consonar)
    - Moclobemide (Aurorix)
- MAO-B (MAO-B inhibitors are not sterically hindered from binding to MAO A and are therefore less selective than MAO A inhibitors)
  - Natural
    - Geiparvarin (Australian Willow)
    - Desmethoxyyangonin (Kava)
  - Synthetic
    - Safinamide and subgroups.
nonselective and irreversable
- Selegiline (Anipryl)
- Rasagiline (Azilect)

TCAs

Amitriptyline (Elavil)
Nortriptyline (Sensoval)

TeCAs

Mirtazapine (Remeron)

NMDA antagonists

Dissociatives such as Ketamine, PCP, MXE or Diphenidine produce a afterglow that lasts 1-2 weeks and has a strong antidepressant effect.

Others

Lithium
Hypericum perforatum (St John's wort)

History

Before the dawn of modern antidepressant research and specialized production, opioids, amphetamines, and methamphetamine were commonly used as antidepressants.

Pharmecutical antidepressants were first discovered accidentally in the 1950s, while research was being undertaken into finding effective treatments for schizophrenia. The first major class of antidepressants available on the market were tricyclics, with MAOIs following around a decade later. While relatively effective in treating patients, there were concerns about the toxicity, side-effects and risks of overdose with these classes of drugs, and they were therefore followed later by the development and release of SSRIs in the late 80s and early 90s, which target serotonin directly.

SSRIs remain in widespread use today accross the world, and since then SNRIs were also developed (combining the receptor actions of tricyclics and SSRIs, without suffering from the previous worries of toxicity etc) and have similarly seen widespread adoption and have been shown in some cases to yield a higher success rate.

More recently, research has gone into alternative means of treating depression. For example, particular inroads have been made studying the anti-depressant effects of dissociative chemicals.

Also in use are natural remedies such as St John's Wort, which is largely understood to have a similar mechanism of action and efficiency rate to SSRIs, with less side effects.

Effects

Positive

Relief of anxiety
Decrease in suicidal thoughts
Improves general quality of life
Improvements in mood

Adverse

Depending on underlying illness may cause mania or increased suicidal thoughts
Sexual dysfunction
Loss of appetite
Hypertension
Sleep Disturbances
Withdrawal
Dietary restrictions (For MAOIs)

Harm Reduction

Drugs that inhibit the reuptake of serotonin tend to dull or cancel the effects of many recreational drugs, while mixing other antidepressants such as MAOIs with certain drugs may be fatal. See the Drug Combinations for more information.

Extreme caution should be taken when using MAOIs, due to their mechanism of action. Eating certain foods containing tryamine can cause *fatal* complications.

Antidepressants cannot be used recreationally.

Do not combine any antidepressants with any medications containing Dextromethorphan (DXM). This can lead to serotonin syndrome which can be a fatal condition.