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Perhaps this can shed some light on the effects of dopamine and serotonin in pots.

Antipsychotic Pharmacotherapy and Orthostatic Hypotension

Gugger, James J. CNS Drugs 25. 8 (Aug 2011): 659-71.

All antipsychotics are associated with orthostatic hypotension,[1-3] although it is more frequent and severe with certain drugs. The incidence of orthostatic hypotension in patients taking antipsychotics is described below; however, comparison between studies should be done with caution due to significant differences in the demographic profile of each study and differing methods of assessment for orthostasis.

The largest source of comparative data comes from the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) trial, a large, federally funded study comparing the relative effectiveness and tolerability of second-generation antipsychotics with first-generation antipsychotics (represented by the mid-potency phenothiazine, perphenazine). Table I shows comparative rates of orthostatic hypotension in patients participating in phases I-III of CATIE.[4-8] Among atypical antipsychotics, clozapine and quetiapine had the greatest incidence of orthostatic hypotension, as high as 24% and 27%, respectively, because of a high affinity for the α 1 -adrenoceptor.

Table I. Percentage of patients reporting orthostatic faintness in phases I-III of the CATIE trial [Table omitted.]

Among the more recently introduced second-generation antipsychotics, iloperidone appears to have the highest incidence of orthostatic hypotension (19.5% compared with 8.3% in patients taking placebo in a pooled analysis of randomized controlled trials),[9] while the incidence of orthostasis with lurasidone and asenapine is less than 2%.[10,11]

There are much fewer data on the incidence of orthostatic hypotension with first-generation antipsychotics, although low-potency (i.e. agents with low potency at the dopamine D 2 receptor) phenothiazine antipsychotics such as chlorpromazine and

thioridazine are generally considered the most likely to cause orthostatic hypotension.[3] The incidence of orthostasis in a report of 515 patients taking chlorpromazine was 8%[12] and it was 14.7% in a randomized controlled trial.[13] Almost no quantitative data exist for higher-potency phenothiazine antipsychotics (perphenazine, loxapine, trifluoperazine, fluphenazine) and thiothixene,[1,3,14-18] but they are generally considered to infrequently cause orthostatic hypotension. In the pooled analysis of iloperidone studies mentioned above, the incidence of orthostatic hypotension with haloperidol (used as an active control) was 15.3% compared with 8.3% for placebo.[19]

Since intramuscular administration generally results in a higher and more rapid elevation of plasma concentrations than oral administration,[20,21] there is likely to be a greater risk of orthostatic hypotension when antipsychotics are administered by the intramuscular route. A large study (n = 2011) evaluated the safety of intramuscular olanzapine relative to other intramuscular antipsychotics (primarily haloperidol). Orthostatic hypotension occurred in 2.4% of patients receiving olanzapine and 4.2% of those receiving any other antipsychotic.[22] Very little data exist for the other intramuscular antipsychotics. In a trial of intramuscular chlorpromazine (dosed at 1 mg/kg with a maximum dose of 100 mg) for the treatment of migraine, 18% (18/100) of patients developed orthostasis.[23] Although the frequency was not defined, orthostasis was the most common adverse effect of chlorpromazine in a trial comparing the efficacy of intramuscular chlorpromazine with intramuscular haloperidol in 50 patients with psychotic agitation; orthostasis was not mentioned as an adverse effect of haloperidol.[24]

On iloperidone (the antipshyotic that causes the most OH)from Wikipedia

...acting upon and antagonizing specific neurotransmitters, particularly multiple dopamine and serotonin receptor subtypes. It is considered an ‘atypical’ antipsychotic because it displays serotonin receptor antagonism, similar to other atypical antipsychotics. The older typicalantipsychotics are primarily dopamine antagonists.

Iloperidone has been shown to act as an antagonist at all tested receptors. It was found to block the sites of noradrenaline (α 2C ), dopamine (D 2A and D 3 ), and

serotonin (5-HT 1A and 5-HT 6 ) receptors. [1] In addition, pharmacogenomic studies identified single nucleotide polymorphisms associated with an enhancedresponse

to iloperidone during acute treatment of schizophrenia. [2]

What I gather from this, is that OH can be caused by blockage of the serotonin and dopamine receptors. Perhaps this is why ssri's help patients with pots.

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New generation antiphsychotic actually calm my body down and help me sleep but impact dreadfully on one of my symptoms -- constipation. First time I took them I was very effected with increasead OH. Next time I took them no problem with OH. It's confusing. But then it was a 3 year break between taking them so maybe my ANS had morphed a little. It can do that, in my case. Eg. Didn't sweat for 6 years, slowly got my sweating ability back and now I sweat too much.


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