Clinical Guide

Research is typically done on single agents, but in practice, medications are most often used in combination. This Clinical Guide offers a way to model/ predict the effects of medication combinations.

Although the theory is complex and supported by hundreds of citations from the medical literature, the practical question is how to treat a patient's symptoms. This document links symptoms in traditional ROS format to apparent purine imbalances (search the site for basic literature review) and medications that may tend to alleviate (or exacerbate) those imbalances.

I recommend writing deficit/excesses from pg1 onto the letters on pg 2, then highlighting the current medications, then considering medication changes.

Each capital letter represents a purine, while lines/arrows represent purine metabolism enzymes that seem to be activated or inhibited by various listed medications, based on a combination of chemical structure and clinical experience. The details of which purine and which enzyme are understated in this chart to provide maximum attention to treatment. There are some purines available as dietary supplements, including SAM-e (X), Inosine (J), and NAD. SAM-e has literature support for psychiatric clinical use.

These charts have helped me to more accurately predict response to complicated combinations of medicines and symptoms. I have been able to watch in detail as symptoms are transformed, then resolved.

My hope is that providers can join me in using this theory as an additional way to formulate symptoms and treatment. Agents noted as unnecessarily opposing each other may be able to be streamlined. Specific agents within current accepted clinical practice may be prioritized in order to more precisely target and treat symptoms. Where traditional recommendations have been exhausted, similarities in chemical structure or apparent effect may point to off-label options.

Discontinuation of antipsychotics:

• avoid contributing to/ worsening Parkinsonian symptoms

• inadequate response despite continued use

• D- deficit is in the lower left-hand corner is the most physiologically pressing, and antipsychotics may function by reducing or blocking D = guanine

SAM-e supplement: 400-800mg BID

• depression treatment/ augmentation strategy unlikely to contribute to Parkinsonian symptoms

• augment purine intake in order to provide raw material (in addition to dietary sources) to address deficits (including O: sleep initiation), since no excesses are available. Represented by X on the Clinical Guide

Add ondansetron 4-8mg BID

• treat potential nausea/ improve appetite

• off-label treatment for anxiety

• low-risk agent with pre-clinical data suggesting improvement for Parkinsonian symptoms PMID 30656239 

• augment conversion to B, C, and D. Connecting ondansetron dose to SAM-e dose reduces risk of secondary I, J, K deficits

Cross-taper antidepressant to sertraline

• trial an alternative SSRI

• different than other antidepressants, sertraline increases flow from beyond-L to more fundamental purines

Add clonidine 0.1-0.2mg BID

• non-BZD treatment for anxiety and sleep unlikely to increase Parkinsonian symptoms

• increase conversion to D, H, and K, addressing the urgent D-deficit (Parkinsonian symptoms) and K deficit (suicidal thoughts and edema). Increasing flow through L will also allow for refilling of non-Z letters beyond L, once the more pressing deficits are filled. (In PD, SAM-e (X) is low prior to treatment, increases following treatment PMID 16340382. Metabolism enzymes moving toward D are upregulated as PD progresses PMID 25597950 )

Late-Stage Changes

Cross-taper sertraline to fluoxetine (selected to address residual OCD symptoms)

• side-effects

• trial a different SSRI

• after pre-L deficits significantly resolved, sertraline-augmented flow was no longer needed and contributed to hyperventilation, which resolved on discontinuation, recurred with accidental restart by cross-cover

Briefly supplement magnesium

• improve sleep/ mood; discontinue due to loose stools

• ensure Q adequacy

Add melatonin for sleep