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Rhodiola rosea’s Place in the GAD Algorithm

Topic: Rhodiola rosea

Principal active chemical: salidroside

Pronunciation:  rho dee OH la roe SAY ah / sal id rho side

Mnemonic phrase: Rodeo Rosie

Mnemonic phrase for salidroside: “Salad Rosies (on the) side”


Rhodiola rosea salidroside psychiatric anxiety treatment by Jason Cafer MD

Rhodiola rosea

❖ Herbal supplement

❖ Adaptogen

❖ Neuroprotectant


Used for:


 ❖ “Burnout” prevention / stress 

 ❖ Generalized anxiety 

 ❖ Depression

 ❖ Extrapyramidal symptoms (EPS)

 ❖ ADHD


The mnemonic: 


Mnemonic phrases for the salidroside component include “Rodeo Rosie’s Salad Rosies” or “Salad rose sides” or “Side salads”.  Some mascots are better than others.  This one is messy because it contains multiple plants. Rhodiola rosea has its own flowers, but we need to associate “rose” from the species name and ~“salad” from the active ingredient, salidroside. 


Rhodiola rosea’s place in a GAD algorithm:


The approach to treating generalized anxiety disorder (GAD) as described by the Psychopharmacology Algorithm Project at Harvard South Shore Medical Program (Osser, 2021) includes these options:


  1. SSRI

  2. Switch to a another SSRI or duloxetine

  3. Augment with hydroxyzine, pregabalin, or a benzodiazepine

  4. Less favored 2nd-line options as monotherapy: 

  • buspirone

  • hydroxyzine

  • pregabalin

  • bupropion

  1. Fourth-line options

  • quetiapine

  • risperidone

  • valproate

  • agomelatine (unavailable in U.S.)

  • lavender oil

  • kava

  • Rhodiola rosea (not to combine with serotonin reuptake inhibitor)


Not included in the algorithm: gabapentin, propranolol, prazosin


Uses:


Clinical evidence is encouraging for use of R. rosea to alleviate stress (Stojcheva and Quintela, 2022). It is included in the Harvard psychopharmacology algorithm for generalized anxiety disorder (Osser, 2021) although overall evidence is of low quality (Xiuzhu et al, 2021). The Carlat Medication Fact Book (2022) did not include R. rosea due to insufficient evidence versus placebo. R. rosea may be effective for mild to moderate  depression, (Darbinyan 2007). Some individuals with ADHD were able to decrease stimulant dosage when R. rosea was added (Carlat Psychiatry Report, 2016).


Related to: 


Other purported adaptogens include ashwagandha and maca. Randomized controlled trials of Rhodiola species include R. rosea (#23), R. crenulata (#8), and R. wallichiana (#8). Neuroprotective mechanisms overlap with lithium.


Pros: 


Several potentially neuroprotective and longevity promoting mechanisms. It extended lifespan of fruit flies, worms, and yeast (Schriner & Lee, et al, 2013). It also prevented cancer in model organisms (Li & Pham, 2017). 


Cons: 


Not regulated by FDA. Complex mixture of phytochemicals, being essentially separate drugs, which may increase risk of complications. Unwanted ingredients such as heavy metals, toxins, or pesticides may contaminate herbal extracts.


InHibitor of multiple CYP enzymes. 


Since some chemicals in R. rosea extract appear to inhibit monoamine oxidase (MAO-A and MAO-B), it should not be combined with a serotonin reuptake inhibitor.  It could potentially induce mania and is not recommended for bipolar disorder. 


Mechanism:  


The adaptogenic mechanism of R. rosea involves the hypothalamic-pituitary-adrenal (HPA) axis by suppressing stress-activated protein kinases. It may influence opioid peptides such as beta-endorphins (Kelly GS, 2001). It has anti-inflammatory and antioxidant effects. 


Side effects: 


Minimal but may include tachycardia


rhodiola rosea interactions

Product choice: 


Herbal quality varies considerably across manufacturers, so it is best to stick with the products used in the actual studies, for instance Rosavin Plus (Ameriden International, 150 mg #90 for $55).  Less expensive options from reputable supplement brands may be acceptable, e.g., Nature's Way, NOW supplements, Life Extension, and Nootropics Depot.


Pure salidroside:


Bioengineered nature-identical salidroside is now available as Landkind LK-01. Since the beneficial effects of R. rosea are largely attributable to salidroside, taking salidroside without the unnecessary chemicals of R. rosea has theoretical advantages. Salidroside itself does not interact with CYP enzymes, OATP, or monoamine oxidase (MAO) as do other R. rosea chemicals.  Since it does not inhibit MAO, pure salidroside could theoretically be combined with a serotonin reuptake inhibitor or taken by individuals with bipolar disorder.  However, efficacy of pure salidroside has not been established. The recommended dose of Landkind LK-01 is 60 mg/day (two 30 mg caps) which costs ~$70/month. 


Landkind salidroside interactions

Dosing of Rhodiola rosea extract: 


R. rosea extract is  often standardized to 1%–2.7% salidroside and/or 2.7% –3.0 rosavin. 340–680 mg/day is the usual dose. Divide BID ~20 minutes before breakfast and lunch.  


Conclusion: 


Although R. rosea may be an effective adaptogen, evidence vs placebo is insufficient. The author generally does not recommend herbal supplements because they contain numerous chemicals with unknown effects and interactions, and may contain toxic contaminants. Although experimental, bioengineered pure salidroside is an intriguing option for treatment-resistant anxiety due to its theoretical neuroprotective and anti-aging effects (Zhong & Han, 2018).





Copyright 2024 CaferMed, intended for prescribers


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