Psychopharmacology of Antidepressants and Antipsychotics

[Petros Agapetos]

The neuroleptic Abilify (Aripriprazole) is approved by the FDA for the treatment of treatment-resistant depression, as an add on treatment to SSRI's (Selective Serotonin Reuptake Inhibitors) etc.

Abilify is a dopamine receptor D2, D3, and D4 partial agonist, with 60% intrinsic activity on D2 receptors. Abilify is an antipsychotic used for the treatment of schizophrenia, schizoaffective disorder, psychosis, mania, bipolar disorder, and depression.

Abilify is also a 5HT1A partial agonist (antidepressant), 5HT2A antagonist (antimanic, antipsychotic), 5HT2C partial agonist, 5HT7 antagonist.

[Petros Agapetos]

It is a verifiably accurate demonstrable fact that antipsychotics cause brain volume reduction (shrinkage). Antipsychotics cause shrinkage within a year. Antipsychotics are like chemical lobotomies. They are chemical restraints *like a mental straight-jacket*.

Almost all antipsychotics cause reduction of dopamine actvity in the mesocortical pathway (Abilify is the only neuroleptic that increases activity here). Antipsychotics are D2 blockers / antagonists. D2 receptors are concentrated on the mesolimbic pathway connecting the midbrain to the nucleus accumbens *the reward center of the brain*. Antipsychotics casue anhedonia, blunting of affect, delay of emotional responses, emotional indifference, apathy, carelessness etc. Abilify, Cariprazinne and Brexiprazole are partial agonist antipsychotics I recommend for the treatment of mania and psychosis etc.. These partial agonists cause less shrinkage than dopamine antagonist antipsychotics. Atypical antipsychotics cause less shrinkage than Typical antipsychotics. This is why long term treatment with antipscyhotics should be contra-indicated but is unfortunately the norm according to psychiatric common wisdom.

[Petros Agapetos]

Abilify
D1 antagonist, very weak
D2 partial agonist, 60%
D3 partial agonist
D4 partial agonist
D5 antagonist, very weak
5HT1A partial agonist (68%)
5HT2A antagonist
5HT2C partial agonist
5HT7 antagonist

[Petros Agapetos]

It is still thought that dopamine mesolimbic pathway is hyperactive in schizophrenia, and that D2 receptors are linked to positive symptoms. There is also growing evidence that, conversely, mesocortical pathway dopamine projections to the prefrontal cortex might be hypoactive (underactive), resulting in hypostimulation of D1 receptors, which may be related to negative symptoms and cognitive impairment.