~ block reuptake of both serotonin and noradrenaline
~ tricyclic antidepressant
Name the side effects of Imipramine.
~ dry mouth ~ impaired muscular control in eye (blurred vision) ~ tachycardia ~ constipation ~ weight gain
depression is caused by a deficiency of monoamine NT e.g. noradrenaline + serotonin
Name the evidence for the monoamine hypothesis.
- drugs that reduce monoamine NT = depression
2. known antidepressants increase monoamine NT = alleviate depression
Name the two discoveries that lead to the monoamine hypothesis.
(Ashcroft + Eccleston, 1960) - decreases serotonin and 5HT were found in brain autopsies of sucide victims
(Axelrod, 1961) - monoamine reuktake blocked by imipramine
Serotonin + depression
serotonin transmission in raphe nuclei is decreased in depressed patients
Problems with monoamine hypothesis 1.
~ Time lag between administration of drug and relief of depressive symptoms
~ antidepressants boost NA and 5HT levels immediately
Problems with monoamine hypothesis 2.
~ Inconsistent findings regarding decreased NA and serotonin in depressed patients
~ maybe changes in NT receptors sensitivity mediate the clinical effects of antidepressant drugs (new theory, needs further investigation)
a.k.a. Selective Serotonin Reuptake Inhibitors e.g. Prozac
~ increase serotonergic activity
~ drugs are 1st choice for treating depression as they produce less severe side effects
Side effects of SSRIs.
~ mild nausea
~ sexual dysfunction (symptoms decrease as treatment progress)
Symptoms of depression.
~ cognitive (feelings of low self-worth + guilt)
~ physical (loss of appetite + insomnia)
~ emotional (persistently sad, anxious + hopelessness)
~ motivational (lack of motivation + aspiration)
~ 1st antidepressant
~ monoamine agonist
~ increases lvls of serotonin, noradrenaline and dopamine by inhibiting monoaminooxidase (MAO)
Name the side effects of Iproniazid.
~ liver damage
~ disfunction in blood pressure control –> hypertensive crisis
How can Iproniazid cause a hypertensive crisis?
~ it is a non-specific MAO blocker
~ blocks MAO-A which when inhibited takes only 10mg of tyramine to cause increased blood pressure
amino acid found in mature cheese, red wine and marmite
SSRI vs SNRI
~ study in healthy volunteers showed there was a right and wrong drug for people
~ compared effects of sertraline (SSRI) and reboxetine (SNRI)
~ some people did well on one and not on the other
~ causes emotional blunting
Antidepressants + age
~ they stop working as well when you get to 65yr+ so augmenting strategies are used
~ common problem in Major Depressive Disorder
A.k.a. serotonin-noradrenaline reuptake inhibitors
~ work similarly to SSRIs
~ 1st antidepressant made, accidentally as meant to treat TB
black the enzyme monoamine oxidase by irreversibly inhabiting it
family of enzymes that metabolise + inactivate monoamine NT
~ creates energised feelings
when normal anti-depressants don’t work, solution is to try combination of SSRIs + other drugs
e.g. symbyax = prozac + zyprexa