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| Theory of Major Depression |
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| Several Brain Circuits become dysfunction in response to stress. Dysregulation of NE and 5HT signalling may contribute. |
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| For anti-depressants, about 3-4 weeks are required before an actual response can be seen . |
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| Disorders like PTSD, OCD, panic attack and others. |
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| Inhibit SERTs generally. Most common type to treat depression, PTSD, OCD. |
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| Inhibit both SERT and NE reuptake receptor. Similar adverse effects compared to SNRIs, but also increase noradrenergic effects. |
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| Atypical antidepressants, inhibits NET and DAT resulting in increased Noradrenergic signal and dopaminergic signalling |
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| Tricyclic antidepressants |
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| Inhibit SERT and NET, elevating serotonin and NET in the cleft. These have muscarinic antagonism as well, and can cause symptoms like dry mouth, blurry vision and a host of others. Narrow therapeutic window. |
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| Usually the last line of defence since it is not a popular choice. Keeps amines alive, but also can result in tyramine, a toxin accumulating. |
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| General term to define a variety of mental disorders. |
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| Prototypic disorder for understanding psychosis and impact of antipsychotic drug treatment. |
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| Structural brain changes in schizophrenics |
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Show problems using prefrontal cortex. Thickness is reduced about 5-10%, neuron size is reduced, though there is no change in number of neurons. Synaptic connectivity is reduced in this area, and there are fewer projections into the thalamus.
In addition, hippocampus shows altered cytoarchitecture. |
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| One hypothesis of why schizo is a thing. This is because antipsychotics block dopamine signalling, drugs that stimulate dopa can product schizophrenic symptoms, Ldopa can exacerbate schizo symptoms, higher levels of dopa receptors measured on brain of schizos, dopamine levels increase during psychotic episodes. |
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| Flaws in dopamine hypothesis |
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Diminished dopamine signaling in specific brain areas is thought to underlie negative symptoms of schizophrenia.
Dopa signal block is immediate, but symptoms persist for days.
Atypical drugs that treat schizo target dopamine receptors. It is possible that schizo acts through other receptors |
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| Since LSD and mescaline produce hallucinations through stimulating 5Ht receptors, it is thought maybe schizo comes out this way. |
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| Strongly block the serotonin receptors, and other receptor types including a weak blockage of Dopa D2 receptors |
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| atypical antipsychotic. Some believe this should be a dopamine system stabilizer. The others are pure antagonists of dopa and sero receptors. This is a partial agonist at D2 and a pure antagonist at sero receptors. Low risk of EPS and metabolic effects. But this may have lower efficacy in some patients |
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| General considerations for antipsychotic drugs |
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| Are a great treatment option for patients, but there is no cure for schizophrenia currently. The goal of the therapy is to alleviate symptoms that can pose danger to patient. These drugs are diverse in structure and show a range of activity. |
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| Typical group antipsychotics |
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| Tranquilizers, neuroleptics. These are the first generation drugs that strongly block Dopa D2. But these have a narrow therapeutic window and may produce EPS |
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| Atypical group antipsychotics |
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| The second generation, moderately or weakly binds Dopa D2. Strongly blocker 5HT. Wider therapeutic window, lower risk for EPS but higher risk for metabolic side effects like weight gain, diabetes, heart disease. |
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Disorders of movement, occurs as a result of blocking D2 receptors. Dystonia, involuntary spasm
Parkinsonisms
Akathisia, need to be in movement
Tardive dyskinesia; Involuntary movement and writing motion of face and tongue, and other extremities. |
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| Atypical antipsychotics are newer and prescribed about 10 times more than typical antipsychotics. Typicals are less expensive, but no single drug is superior when safety and efficacy are considered. For patients with history of diabetes or dyslipidemia, one of the typical antipsychotics may work best. |
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| Antagonists of 5HT2 receptor. Inhibiting this receptor is associated with substantial antidepressant effects , antianxiety and antipsychotic. Also inhibits SERT. Side effects are muscarine like. |
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| Block metabolism of NE, serotonin and other amines. Rarely used for managing depression since they can become toxic interacting with other compounds like those that has tyramine related accumulation. |
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| Can cause tyramine levels to reach dangerous levels |
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| selective inhibition of this show low efficacy in treating depression unless both are inhibited. Generally these are avoided. |
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