History and Development of Antidepressants

1950s: The Origins

Discovery of two drugs that sparked the antidepressant market:
- Iproniazid: Intended to treat tuberculosis.
  - 1952 trial: Improved moods of patients with depression.
- Imipramine: Intended to treat allergic reactions.
  - 1956 trial: Observed mood improvements.
Both drugs affected neurotransmitters called monoamines.

Concept: Depression caused by insufficient monoamines in brain synapses.
Iproniazid and imipramine increased the availability of monoamines.
Side effects: headaches, grogginess, cognitive impairments (memory, thinking, judgment).

1988: Fluoxetine (Prozac) introduced as the first Selective Serotonin Reuptake Inhibitor (SSRI).
- Blocks reabsorption of serotonin, increasing its availability in the brain.
- Fewer side effects compared to older antidepressants.
Marketing emphasized the dangers of depression and reduced stigma.

1990s: Increase in people treated for depression.
- Decline in psychotherapy and other treatments.
Current understanding: A combination of psychotherapy and antidepressants can be more effective.

Effectiveness varies:
- Not everyone responds to SSRIs.
- Some respond better to different drugs or to no medication.
- Combination therapy can be more effective.
Unclear mechanisms:
- Monoamine levels change quickly, but benefits take weeks.
- Mixed outcomes: Some never relapse, others do.
The chemical imbalance theory is incomplete:
- Antidepressants' effect on serotonin doesn't confirm serotonin deficiency as the cause.
- Analogy: Steroid creams treat rashes but don't imply a steroid deficiency.