Ant-depressants as treatment for Depression

Basic assumption for treatment by antidepressants

Depression is caused by low levels of monoamine neurotransmitters (5HT, NA, DA)

• Drugs typically block reuptake leaving more in the synapse to bind to receptors, increasing activity

MAOIs function and side effects

• Block action of monoamine enzymes (MOA) that break down neurotransmitters in the synaptic gap

• Irreversible high blood pressure

• No chocolate, cheese or SSRIs

Tricyclic antidepressants function and side effects

• Increase 5HT, NA and to some extent DA

• Blocks reuptake

• Increases mood, motivation and energy

• Blurred vision, inc. heart rate, disorientation

Selective Serotonin Reuptake Inhibitors function and side effects

• Preferred treatment option

• Increase 5HT by blocking reuptake

• Less severe side effects of nausea, weight change, headaches, fatigue

Atypical antidepressants

• More tailored

• Can increase 5HT, NA, DA

• Example: SSNIs → Serotonin-Noradrenaline reuptake inhibitors

• Also help anxiety disorders or OCD

• Nausea, nervousness, dry mouth

General supporting evidence

• Drugs that alter levels of 5-HT and NA are effective in treating depression in 60%~ of cases

• Some evidence suggests mood disorder patients have abnormal levels of NA and 5-HT

Research evidence for 5-HT: drugs and anti-depressants

• MDMA (ecstasy) increases serotonin in the cleft and produces feelings of euphoria

• Antidepressants work by blocking reuptake so there is more in the cleft to stimulate post synaptic receptors and elevate mood

BUT some researchers believe anti-depressants cause a placebo effect Kirsch et al. 2002

Research evidence for NA: antidepressants

• Versani at al. 1999: double blind trial using NRIs and placebo drug

  • Marked improvement in the mood of patients with depression compared to control

  • BUT don’t work with all depressed individuals

• Andreoli et al. 2002

  • Anti-depressants that increase NA are just as effective as those that increase 5-HT

  • Both potential explanations

Supporting evidence

Geddes et al. 2013

• Drug treatment for depression had a relapse rate of 18%

• Placebo group had a relapse rate of 41%

Contradictory evidence

• Treatment aetiology fallacy: just because antidepressants that increase these neurotransmitter levels work, doesn’t mean they are the cause

• Delago 2000: antidepressant drugs are effective, consistent with MA hypothesis, there is a lack of convincing evidence of a primary dysfunction of the MA system in depressed individuals

• Mariana Angoa-Perez et al. 2014: bred mice without the gene for the enzyme tryptophan (precursor for 5-HT production)

  • Found no signs of depression and no response to antidepressants