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I found this at wikipedia: "Its antipsychotic effects are likely caused by D2 and/or 5-HT2A antagonism, whereas its antidepressant effects at lower doses may be mediated by preferential D2/D3 autoreceptor blockade, resulting in increased postsynaptic activation."

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In low doses, maybe not for OCD because of the increased dopamine release (see @notloki's comment regarding D2/D3 autoreceptor blockade). 

Higher doses are required for "antipsychotic" effects, but the ratio of 5-HT2A-to-D2 affinity is so high that there won't likely be any relevant 5-HT2A blockade at any doses and it'll be solely D2 blockade that is doing any relevant antipsychotic activity (D3 blockade too).

It's also a pretty potent H1 antagonist too, so watch out for weight gain.

Watch out for hyperprolactinemia with flupenthixol (extremely potent D2 antagonism without 5-HT2A antagonism to cause dopamine release in the tuberoinfundibular dopamine pathway to counteract it causes increased prolactin).

As far as antipsychotics go (at least in the US), ones that are most commonly used for OCD augmentation treatment are:

  • First generation
    • haloperidol (Haldol) (especially with comorbid tics/Tourette's disorder) (generally poorly tolerated, requiring β-blockers and/or anticholinergics for EPS)
  • Second generation
    • risperidone (Risperdal) (infamous for causing hyperprolactinemia as well due to excessive targeting of D2 receptors in the pituitary gland, but very low doses are preferential for 5-HT2A inverse agonism over D2 antagonism since there is a 21:1 ratio of selectivity for affinity for 5-HT2A receptors over D2 receptors, and 5-HT2A/2C antagonism/inverse agonism has anti-obsessive effects as well)
    • paliperidone (Invega) (metabolite of risperidone IIRC... Just about as bad for causing high prolactin as risperidone is...)
    • aripiprazole (Abilify) (I seem to remember you can't tolerate this one)
    • olanzapine (Zyprexa) 
    • quetiapine (Seroquel/Serooquel XR)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343405/

I would also be willing to say, based on the affinities for the various receptors, these antipsychotics would also be effective (please forgive me as I don't know the availability of these antipsychotics in your country, and I've yet again forgotten where you live as I have poor memory):

  • First generation
    • fluphenazine (Prolixin) (sort of the phenothiazine equivalent to haloperidol, roughly equipotent mg-per-mg; potent D2 antagonism, slight 5-HT2A antagonism)
    • loxapine (Loxitane) (in low doses, 5-HT2A antagonism > D2 antagonism and behaves like an atypical; produces the tetracyclic antidepressant, amoxapine (Asendin) as an active metabolite, which acts as a selective norepinephrine reuptake inhibitor + 5-HT2A/2C antagonist > D2 antagonist)
    • perphenazine (Trilafon) (perhaps? potent D2 antagonism, slightly relevant 5-HT2A antagonism)
    • thiothixene (Navane) (related to flupenthixol IIRC... extremely potent D2 antagonism)
    • trifluoperazine (Stelazine) (potent D2 antagonism, slight 5-HT2A antagonism; quite a magical medicine from my experience, very worth trying!)
  • Second generation
    • Saphris (asenapine) (5-HT2A/2C antagonism > D2/3/4 antagonism)
    • Rexulti (brexpiprazole) (5-HT1A partial agonism @ 60% > D2L partial agonism @ 43% + 5-HT2A antagonism nearly the same affinity as D2L partial agonism)
    • Vraylar (cariprazine) (D3 partial agonism @ 60% > D2L partial agonism @ 40%)
    • ziprasidone (Geodon) (5-HT2A > D2 antagonism + 5-HT2C antagonism/partial agonism and 5-HT7 antagonism near D2 antagonism affinity + "mini-SNRI")

Have you ever tried the SSRI fluvoxamine (Luvox)? It's supposed to be the go-to SSRI for OCD. There's also the TCA, clomipramine (Anafranil), which was horrible for me, but seems to benefit others quite well.

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Wow @clinic I just looked at your whole med list for the first time and you've really seen the med-go-round, and done all the usual suspects. Curious, do you need an OCD med that will also help psychosis or are you just looking for an OCD-killer add-on (which may open the playing field a bit.) 

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Posted (edited)

In addition to powerful D2 actions, flupentixol has anti-serotonergic (5-HT2) and anti-adrenergic (predominantly a1) actions, but its activity at cholinergic sites is too little to be clinically relevant (Fig. 1). It can therefore be associated with hypotension on first oral exposure and with extrapyramidal side-effects, though with gradual introduction and doses kept low, it is generally well tolerated.b Flupentixol has the greatest D1 antagonist activity of all the older antipsychotics. The significance of this is unclear for, clinically, it does not stand out as correspondingly different – apart from in one possible regard. Flupentixol has long been associated in low dose with antidepressant and anti-anxiety actions (Reiter 1969; Hall 1973; Predescu 1973; Frolund 1974; Gruber 1991). Most reports are anecdotal (e.g. Trueman 1974; Becker 2002) or find easy explanation in different dose regimes between flupentixol and comparator drugs (Wistedt 1983), but a clinically impressive antidepressant action has been demonstrated in good trials. In a two-arm non-placebocontrolled study, Young et al (1976) found that in mild to moderate depression, flupentixol had antidepressant efficacy comparable to that of amitriptyline, with greater anti-anxiety effects. In terms of quality of life, Hertling et al (2003) found that people with schizophrenia treated with flupentixol felt subjectively more relaxed and better able to deal with stress than those on risperidone. We have seen similar claims for many early antipsychotics, especially when the search for marketable indications was active (Owens 2012, this issue). However, a reputation for beneficial mood actions must surely have stuck to flupentixol longest and most consistently – perhaps sufficiently so to accept the claim as valid. This is the only older antipsychotic with UK approval for use in depression. In line with recent trends, such affective benefits have been attributed to serotonergic actions (Becker 2002), but autoreceptor effects – presynaptic D1 antagonism diminishing tonic inhibition of the transmitter synthetic enzyme tyrosine hydroxylase (or 3-monooxygenase) – highlighting as they do a prominent action of flupentixol, would seem worthy of consideration. However, the notion that flupentixol’s clinical pharmacology might allow it to be considered a ‘partial atypical’ antipsychotic (Rachid 2004) is to turn the taxonomical embarrassment of ‘atypicality’ (Owens 2008) seriously surreal.

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Cis-Flupenthixol binds with high affinity to dopamine D1-, D2-, D3-, 5-HT2A- and alpha 1-adrenergic receptors. • Its in vitro receptor profile differs from that of haloperidol and shows similarities with those of atypical neuroleptics. • It reduces positive and negative symptoms in schizophrenic patients as evaluated in a oneyear follow-up study. • Cis-flupenthixol shows -particularly at standard dosages and lower - a reasonable good tolerability and safety profile. • Based on these and other properties cis-flupenthixol may be classified as a partial atypical neuroleptic.

Edited by morpheus

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I spoke with another pdoc, he said there is risk of tardive dyskinesia with flupentixol. So im not going to take it

On 6/23/2020 at 5:40 AM, Iceberg said:

Wow @clinic I just looked at your whole med list for the first time and you've really seen the med-go-round, and done all the usual suspects. Curious, do you need an OCD med that will also help psychosis or are you just looking for an OCD-killer add-on (which may open the playing field a bit.) 

Yea im looking for med without any drug interaction for ocd. No i dont need ocd med which helps psychosis. I want it to just fix ocd.

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Posted (edited)
On 6/23/2020 at 3:24 AM, mikl_pls said:
  • Have you ever tried the SSRI fluvoxamine (Luvox)? It's supposed to be the go-to SSRI for OCD. There's also the TCA, clomipramine (Anafranil), which was horrible for me, but seems to benefit others quite well.

I cant take fluvoxamine as it doubles the plasma levels of clozapine. Im looking for med for ocd which does not have drug interactions.

How about desvenlafaxine ?

Edited by clinic

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There will always be interactions. Tardive dyskinesia is going to be listed in every AP,AAP's PI. It is the incidence that matters.

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