Warning: If you recently started taking an antidepressant and have noticed a significantly worsening mood, including thoughts of suicide, please immediately leave your computer and either get in touch with your doctor or the nearest hospital. Thank You.

Some claim that pharmaceutical antidepressants are perhaps only effective when depression is severe. For depression of a moderate or mild quality, Habits to Decrease Clinical Depression may suffice. It’s better to not treat depression with drugs, if they’re not completely necessary,

Generally, antidepressants take from two to six weeks to work fully. However, it could take up to 12 weeks. Initial benefits can manifest as early as a few days after starting treatment. If it doesn’t work, no need to fret. There are over 20 antidepressants.

Excluding people who drop out of treatment, 60%-70% of patients taking antidepressants find that their life significantly improves. There are many classes of pharmaceutical antidepressants. The image below depicts how our body naturally releases, then captures back (reuptake), a few brain chemicals that are highly associated with depression (serotonin and norepinephrine).

  • SSRIs (serotonin reuptake inhibitors)
    • These chemicals block serotonin from being funneled back into the presynpatic serotonin transporter (SERT)
      • When that is done, there is more serotonin in the synapse
      • More serotonin in the synapse means more serotonin binding to its receptor
    • Examples include Prozac (fluoxetine), Zoloft (sertraline), Paxil (paroxetine), and Celexa (citalopram)
    • Some, such as Prozac, may be uplifting
    • Paxil binds with greatest strength to SERT, which may be why many think it’s the most useful SSRI for anxiety and panick
    • SSRIs are also used in the treatment of
      • Obsessive-compulsive disorder
      • General anxiety disorder
      • Social anxiety disorder
      • Panic disorder
      • Post-traumatic stress disorder
      • Bulimia
      • Premature ejaculation
      • Headaches
      • Premestrual dysphoric disorder

  • SNRIs (serotonin-norepinephrine reuptake inhibitors)
    • SNRIs block serotonin and also norepinephrine from being removed by the reuptake pump
      • Same as SSRIS, more of these chemicals in the synapse means greater overall binding to their receptors
    • There are three SNRIs: Effexor (venlafaxine), Pristiq (desvenlafaxine), and Cymbalta (duloxetine)
    • Also used for
      • General anxiety disorder
      • Panic disorder
      • Social phobia
      • Various forms of physical pain
      • ADHD

  • the NDRI (norepinephrine-dopamine reuptake inhibitor) Wellbutrin/Zyban
    • Instead of acting on serotonin, inhibits reuptake of norepinephrine and dopamine
    • Not as associated with sexual malfunction as the SNRIs and SSRIs
    • Dopaminergic activity is weak, almost insignificant at doses at and below 200mg
    • For depression, extended release doses ranging from 100mg to (rarely) 600mg
      • Usually between 300mg and 450mg
    • Used also for
      • ADHD
      • Smoking cessation
        • Blocks a part of the nicotine receptor
        • 25mg instant release Zyban pills
      • Bipolar depression
        • Lower chance of causing mania than the SSRIs and SNRIs
  • Tricyclics (also known as Heterocyclics)
    • Alters the binding of various chemicals to their receptors 
      • Serotonin-norepinephrine reuptake inhibition
        • Some, such as Elavil, work more on serotonin than on norepinephrine
        • Others, like Pamelor, have noradrenergic (norepinephric) activity that overshadows their serotonergic activity
      • Histamine (H1) receptor blockers
      • Adrenergic receptor blockers
      • Muscarinic receptor blockers
    • Also used for
      • Anxiety
      • Insomnia
      • Headaches
      • Obsessive-compulsive disorder
      • Panic disorder
      • Some forms of physical pain
    • May produce more side effects than newer antidepressants
    • More dangerous than other antidepressants

Here we have a chart detailing how tricyclics and conventional SNRIs meet, and the effects of the additional receptor systems that tricyclics affect.

This depiction shows (very roughly) how things might actually look like

  • Atypical antidepressants
    • Viibryd
      • SSRI
      • Also works similarly to Buspar, the anti-anxiety medication
        • 5-HT1a partial agonist
        • 5-HT is synonymous to serotonin
    • Remeron (mirtazepine)
      • Non-addictive use as a sleep aid
      • SNRI
      • increases appetite
      • Blocks some serotonin sites to reduce anxiety, sexual dysfunction, and stimulate appetite
      • Works faster than other antidepressants
      • Low risk of sexual dysfunction
  •  
    • Oleptro (trazadone)
      • non-addictive use as sleep aid
      • SSRI
      • Activates some serotonin sites
      • Prevents activation at some serotonin sites
      • Has a metabolite that may be responsible for many therapeutic effects
  •  MAOIs (monoamine oxidase inhibitors)
    • Monoamine neurotransmitters are serotonin, dopamine, norepinephrine (and the metabolite of norepinephrine: epinephrine)
    • Two kinds of monoamine oxidase: monoamine oxidase A and monoamine oxidase B
      • MAO-A increases serotonin, dopamine, and epinephrine levels
      • MAO-B increases dopamine, norepinephrine, and trace amine levels
      • Must have MAO-A inhibition for antidepressant effect
    • Parnate, Nardil, and Emsam
    • A strict diet must be adhered to, otherwise one may have a hypertensive crisis and a stroke
    • Most useful in atypical forms of depression
    • Also treat anxiety disorders
    • Parnate
      • Especially useful for psychotic depression
      • Stimulating
      • Has more MAOI on the B form, than on the A form
    • Nardil
      • Also raises GABA levels, which makes it especially useful for anxiety
      • May be sedating
      • Has more MAOI on the A form, than on the B form
    • EMSAM
      • Old parkinson’s medication, selegiline, in patch form (transdermal)
      • No need to follow diet very strictly at 6mg patch, but must at 9mg and 12mg form
      • Stimulating, though less effective than parnate
      • May be an anti-aging agent for the brain
      • Fewer side effects than the tricyclics
    • This class is very effective
    • Must not use many other medications while on them, such as cold medicine. Please consult the chart below for dangerous drug interactions with antidepressants. It’s not worth your life!

Treatment-resistant depression is diagnosed when one has failed to respond to at least two other antidepressants, spending six to 12 weeks on each at the maximum dose that is tolerable

There are FDA-approved therapies for such, as add-on medications…

  • Abilify (aripiprazole)
    • Also used for schizophrenia and bipolar disorder, but at much higher doses
    • D2 partial agonist, keeping dopamine levels within a range
    • Also a 5-HT1a partial agonist, working as an anxiolyitc (anti-anxiety agent)
    • Usually stimulating at doses for depression
    • Mood-stabilizing traits
  • Seroquel (quetiapine)
    • Also used for schizophrenia, but more so for bipolar disorder
    • Can be very sedating
  • Symbyax
    • A combination of two medications, olanzapine and fluoxetine
    • Antidepressant and tranquilizing effects
  • Vagus nerve stimlation
  • Deplin
    • a form of vitamin B
    • produces red blood cells
    • termed a “medical food”

Other common, though not FDA-approved, methods of medicating treatment-resistant depression exist

  • Electroconvulsive therapy
    • Usually six to 12 treatments
    • Much more safe these days
  • Transcranial magnetic stimulation
  • Ketamine infusion therapy
    • Illegally used for recreational purposes
    • Not used at doses that could cause hallucinations
    • NMDA antagonist and AMPA receptor modulator
  • Lithium
    • The “gold standard” for treating bipolar disorder
    • Has a variety of actions, such as increasing tryptophan (the precursor to serotonin) synthesis
  • Lamictal
    • Also used for bipolar disorder
    • Has ra reputation for working more on depression than mania
    • Usually has no side effects
  • Buspar
    • A 5-HT1a partial agonist
    • Non-addictive agent used for anxiety
  • Tegretol
    • Also used an an anticonvulsant (stops seizures)
  • Cytomel
    • used for an underactive thyroid
  • A MAOI plus another antidepressant
    • Must be extremely careful, monitoring for serotonin syndrome and hypertensive crisis

If everything else has failed after complete treatment adherence (including therapy and drug abstinence), some psychiatrists may try the following augmentations (combining an antidepressant with another medication). They all work fast, but also have the potential to be very addictive.

  • Benzodiazepines
    • Short-term
    • Very difficult to stop using if treatment exceeds a month
      • Notoriously long and painful withdrawal syndrome, see PAWS
  • Stimulants
    • Occasionally useful for lethargic depression
    • particularly useful in older patients
    • Also used for ADHD, weight loss, and narcolepsy
    • Can maybe be added to MAOI treatment with extreme caution by an expert
    • Methylphenidate, the norepinephrine-dopamine reuptake inhibitor (NDRI)
    • Amphetamine, the norepinephrine-dopamine releaser, reuptake inhibitor, and (at high doses) monoamine oxidase inhibitor (NDRA, NDRI, and MAOI)
    • Modafinil and Armodafinil, various actions, weak norepinephrine-dopamine reuptake inhibitor (NDRI)
      • Addiction and negative side effects less probable than that of other stimulants
  • Opioids
    • The absolute last line of defense before surgery
      • Very high abuse potential
    • Also useful for opiate addiction, anxiety, and insomnia
    •  Suboxone, the partial agonist at opiate receptors
    • Ultram, which also has direct effects on serotonin and norepinephrine