Parapsychosis

Parapsychosis is a most commonly observed within Borderline Personality Disorder (BPD): PMID 23168909 or PTSD, although it may also contribute to symptoms within psychotic diagnoses.

Patients with parapsychosis are sometimes able to discern that their experiences are not real, even in the midst of their peak symptoms. Sometimes logic is preserved and supporting evidence is misremembered into existence.

Parapsychoses most often occur in the context of dissociation and some level of amnesia, and may fluctuate significantly over the course of hours. Dissociative identity disorder may be a subcategory of parapsychosis.

Parapsychoses differ from malingered/ instrumental psychotic complaints, although both may present as psychotic complaints without reality-testing impairment. "Attention-seeking" blurs this important distinction. Even in limited form, e.g. not being able to discern memories from vivid dreams, parapsychosis can be devastating. The real suffering attributable to parapsychosis deserves our best efforts to ameliorate, not dismiss.

Malingered symptoms do not coalesce into a syndrome, since the manufactured description of symptoms can vary widely.

We have previously discussed the correlation between X-derivatives/ analogues and dissociations, exemplified by the mostly-historical psychiatric practice of using amobarbital to induce dissociative episodes.

We have also discussed buspirone as a xanthine-similar compound that contributes to dissociation at low doses and psychosis at at high doses: PMID 22290846. Z-drugs demonstrate both adverse effects: dissociation and psychosis, and are xanthine-similar.

Some xanthine-similar compounds have been associated primarily with psychosis.

Xanthine production includes contributions from both G-derivatives (guanine via guanase) and I-derivatives (hypoxanthine via xanthine oxidase). These two contributing pathways roughly correspond to parapsychosis and non-manic/ schizophrenic psychosis.

In this formulation of parapsychosis, a patient may have excess I-derivatives, which, converted to excess xanthine, presents as dissociative symptoms, sometimes to the extent of guanase inhibition and secondarily excess guanine, presenting as parapsychosis.

The psychosis associated with xanthine-similar levetiracetam is described as "schizophrenia-like": PMID 32920785, distinct from the manic-similar symptoms of guanosine analogues: e.g. PMID 17651180.

Perceptual disturbances induced by xanthine-similar hallucinogens like psilocybin approximate parapsychosis: perceptual distortions with varying levels of reality-testing impairment and amnesia.

Outside of psychotic diagnoses, parapsychoses may be described as poorly formed: incoherent noises or whispers in the background rather than clear voices; searching for connections, rather declaring a paranoid plot.

Some typically psychotic presentations (persistent over days, with dense reality-testing impairment) also include poorly formed or dissociative components: amnesia for recent events, delusional content including a portal to the unknown to be entered by particular action (sometimes at high-speed resulting in collisions), or a description of multiple realities or dimensions pressing in on the patient. Capgras delusion may fall within this category as a sense that something is off, without conviction as to how or why a particular person was replaced.

Poorly formed psychotic symptoms may represent a subtype of schizophrenia-like psychosis amenable to treatments addressing the inosine-contribution to xanthine.

Oxcarbazepine (OXC) is a prodrug for the active metabolite eslicarbazepine: PMID 22612290. Carbamazepine (CBZ) is metabolized into its likely active product. Note that other medications that share this structure, including cyclobenzaprine and cyproheptadine, are likely to form similarly active metabolites.

OXC/CBZ have an ACE inhibitor-like effect: PMID 22832858 discussed previously. Note the hypoxanthine-similar chemical structure shared by ACE inhibitors and CBZ/OXC active metabolites. Decreased xanthine due to ACE inhibitors is evident in increased insulin sensitivity: PMID 1284142, 18326972 and decreased cardiac risk, properties that may not be shared by angiotensin II receptor blockers: PMID 15701766 or aldosterone receptor blockers such as spironolactone and eplerenone.

I recently attended a case with new onset psychosis with Capgras delusion (despite days of low-dose risperidone) and HTN.

Upon assuming care, I replaced risperidone with oxcarbazepine, trusting the ACEi effect for HTN, with brief lorazepam for SJS prophylaxis and NaCl supplement to prevent hyponatremia. Capgras resolved within 24 hours and psychosis resolved within 48 hours, but recurred after lorazepam course: by replacing with guanfacine, psychosis and HTN resolved, and the patient returned to graduate-degree level work.

Inosine-similar duloxetine has preliminary trials demonstrating benefit in Borderline Personality Disorder (BPD): PMID 18719047 and has been helpful in cases with dissociation and/or parapsychosis. Consistent with this use of duloxetine and our proposed statin mechanism, statin use is associated with positive interpretation of stimuli: PMID 35606186.

Low-dose loxapine and chlorpromazine also show preliminary benefit in BPD: PMID 7040351. Due to seizure risk, chlorpromazine should be slowly titrated.

In my experience, patients with nightmares, flashbacks, hypervigilance, or easy startle may find these drugs intolerable unless they are paired with an alpha-agonist/ anti-cortisol like clonidine or guanfacine, an accepted treatment in PTSD: PMID 26322115.

Quetiapine and phenothiazines like chlorpromazine substitute sulfur for oxygen (similar behavior) and have been helpful at low dose for parapsychosis and for cases where therapeutic-dose antipsychotic is indicated. We previously discussed the reduced seizure risk with fluphenazine compared to other phenothiazines.

Despite some structural similarity between loxapine and asenapine, asenapine's efficacy in schizophrenia-like psychosis is documented to be poor and it is accordingly not indicated for schizophrenia in the UK: PMID 26599405. Without the matching N-substitution, it may not bind therapeutically in this orientation.

Inosine-similar duloxetine shares risk of hyponatremia with CBZ/OXC, especially in the context of other anti-aldosterone therapies: PMID 30799349. Duloxetine directly increases ADH: PMID 30799365 whereas CBZ/OXC does not: PMID 12112108: CBZ/OXC increases sensitivity to ADH and blocks aldosterone.

Note that we have now associated I-derivatives with blood pressure and HPA in multiple different ways.

There is an unknown mechanism by which the hypothalamus signals the pituitary: it may be that purine balance within hypothalamic cells participates in signal transduction.

Note that I-derivatives are now tightly connected with major mechanisms of hypertension and antihypertensives.

I strongly recommend trending blood pressure by mean arterial pressure as a marker for medication regimen sustainability: target MAP <93.

Those reviewing Metabolic Syndrome will note that purine nucleoside phosphorylase is the same proposed target for both statins and ACE inhibitors. Similar physiology has been confirmed and is shared with doxycycline, which shares the hypoxanthine-similar chemical structure: PMID 34503440.

There is a subset of patients who present with dissociative symptoms/ parapsychosis who demonstrate difficulty maintaining blood pressure suggestive of low hypoxanthine levels: naltrexone, as a pro-cortisol: PMID 22575355 may be a particularly helpful adjunctive for these patients or in treatment-resistant cases. This might be expected in cases of inadequate inosine-guanosine kinase activity or excessive xanthine oxidase activity. Naltrexone is an accepted therapy for dissociative symptoms: PMID 22002175.