Antidepressants: SSRI, SNRI & Tricyclic Antidepressatns. Citalopram Prozac Amitriptyline
2:20 – Mechanism of Antidepressants
3:16 – General Principles of Antidepressant Use: Suicide, Mania & Serotonin Syndrome
7:51 – Tricyclic Antidepressants
9:10 – TCA Side Effects
10:40 – SSRIs
11:47 – SSRI Side Effects
13:01 – SNRIs
13:33 – Atypicals: Bupropion, Mirtazapine & Trazadone
Antidepressant mechanism – One hypothesis for the pathophysiology of depression is that it is due to low levels of monoamine neurotransmitters (mainly serotonin, norepinephrine and dopamine). That is why antidepressants aim to increase the levels of these neurotransmitters in the synaptic cleft. They do this by slowing the reuptake of the neurotransmitters so that they stay in the cleft longer and interact with post synaptic receptors more often. The first drugs in this group were non-specific and increased all of the monoamines, which lead to lots of side effects and safety issues related to toxicity. Newer antidepressants are more selective and mostly only effect 1 or 2 monoamines.
Unfortunately, antidepressants take at least a month to start working. Good patient education about the delayed onset of effect and close monitoring of the patient during this initial period is extremely important. Patients can become hopeless if they expect the drug to start working right away. This may be one reason why antidepressants are associated with suicide, especially in patients 25 years old and younger. Another proposed mechanism is that a depressed person may have the energy to carry out their suicide once the medications start to work. There is now a black box warning for suicide on antidepressants. Some psychiatrists argue that they don’t actually see this association with suicide in clinical practice, and that the thing that really increases the risk for suicide is not treating a depressed person with the proper medications. However, it is still standard practice to have a close follow up with patients you are starting on antidepressants. Usually this will involve a follow up visit about 2 weeks after the medication is started. At this visit the drug will not have started working yet so you can’t evaluate efficacy, but you can monitor for side effects like suicidality. Another serious side effect you have to be on the lookout for soon after initiating treatment is mania. If a bipolar individual is incorrectly diagnosed as having depression, an antidepressant may induce a manic episode.
Another very serious side effect that has to be considered for antidepressants is Serotonin Syndrome. This usually occurs when you combined multiple antidepressants at the same time or combine an antidepressant with another medication that increases serotonin such as dextromethorphan or an opioid. It presents with tremor, diaphoresis, tachycardia, flushing and hypertension. If not corrected it can progress to delirium, AMS and death. Treatment includes medication cessation and the use of Cyproheptadine (a serotonin antagonist). In order to prevent this from happening you should have about a month “Wash Out” period when you are switching between antidepressants. So you taper the 1st medication down and then stop it, give the patient at least a month with no antidepressant and then start adding the new medication slowly.
Most side effects begin immediately after starting the medication, but diminish over the course of a month. This is another reason why patient compliance is poor with these meds. It makes them sick and the drug doesn’t work during the first few weeks. However, if they can stick with it the medications will likely start working and the side effects will diminish over time. A principle that applies to all of the antidepressants is “start low and go slow.” This means that you start with a lower dose and slowly increase it in order to decrease side effects and increase patient compliance. The dose you start the patient on may not even be at a therapeutic level, but every month or so you can increase the dose a bit.
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