Adjuvant palmitoylethanolamide therapy with risperidone improves negative symptoms in patients with schizophrenia: A randomized, double-blinded, placebo-controlled trial

Salehi, Anahita; Namaei, Parsa; TaghaviZanjani, Fateme; Bagheri, Sayna; Moradi, Kamyar; Ardakani, Mohammad-Reza Khodaei; Akhondzadeh, Shahin

doi:10.1016/j.psychres.2022.114737

Cited by 16 publications

(13 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ultimately, 44 studies comprising 3358 participants and 45 augmentation treatments met the inclusion criteria. 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 The characteristics of the included studies are presented in Table 1 . The mean age of the participants was 39.5 (standard deviation = 5.8) years, and 33.5% (1124/3358) of participants were women.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive evaluation of 45 augmentation drugs for schizophrenia: a network meta-analysis

Etchecopar-Etchart,

Yon,

Wojciechowski

et al. 2024

eClinicalMedicine

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Comprehensive evaluation of 45 augmentation drugs for schizophrenia: a network meta-analysis

Etchecopar-Etchart,

Yon,

Wojciechowski

et al. 2024

eClinicalMedicine

View full text Add to dashboard Cite

“…Three human studies have addressed this area ( Table 1 ) using similar but not overlapping methodologies in terms of study population [chronic schizophrenia (SCZ) patients ( 52 ), bipolar disorder (BPAD) patients with manic symptoms ( 53 ), Parkinson's disease (PD) patients ( 51 )], PEA formulation [oral native PEA ( 52 , 53 ), oral Ultramicronized (um)-PEA ( 51 )], PEA dosage [600 milligrams (mg) daily ( 51 ), 600 mg twice/daily ( 51 – 53 )], and PEA period of exposure [6 weeks ( 53 ), 8 weeks ( 52 ), 12 months ( 51 )]. Apart from a single study lacking a controlled condition ( 51 ), all studies adopted a randomized, double-blind, placebo-controlled design ( 52 , 53 ). Overall, results indicated a beneficial effect of PEA adjunctive therapy on residual negative and general psychopathological symptoms, but not positive symptoms, of risperidone-treated SCZ patients ( 52 ), as well as on manic symptoms of lithium- plus risperidone-treated BPAD patients ( 53 ).…”

Section: Resultsmentioning

confidence: 99%

“…Apart from a single study lacking a controlled condition ( 51 ), all studies adopted a randomized, double-blind, placebo-controlled design ( 52 , 53 ). Overall, results indicated a beneficial effect of PEA adjunctive therapy on residual negative and general psychopathological symptoms, but not positive symptoms, of risperidone-treated SCZ patients ( 52 ), as well as on manic symptoms of lithium- plus risperidone-treated BPAD patients ( 53 ). Coherent data emerged regarding depressive symptomatology, which did not appear to be improved in both SCZ and BPAD patients treated with PEA add-on as compared to placebo ( 52 , 53 ).…”

Section: Resultsmentioning

confidence: 99%

Questioning the role of palmitoylethanolamide in psychosis: a systematic review of clinical and preclinical evidence

Bortoletto,

Piscitelli,

Candolo

et al. 2023

Front. Psychiatry

View full text Add to dashboard Cite

IntroductionThe endocannabinoid (eCB) system disruption has been suggested to underpin the development of psychosis, fueling the search for novel, better-tolerated antipsychotic agents that target the eCB system. Among these, palmitoylethanolamide (PEA), an N-acylethanolamine (AE) with neuroprotective, anti-inflammatory, and analgesic properties, has drawn attention for its antipsychotic potential.MethodsThis Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-compliant systematic review aimed at reappraising all clinical and preclinical studies investigating the biobehavioral role of PEA in psychosis.ResultsOverall, 13 studies were eligible for data extraction (11 human, 2 animal). Observational studies investigating PEA tone in psychosis patients converged on the evidence for increased PEA plasma (6 human) and central nervous system (CNS; 1 human) levels, as a potential early compensatory response to illness and its severity, that seems to be lost in the longer-term (CNS; 1 human), opening to the possibility of exogenously supplementing it to sustain control of the disorder. Consistently, PEA oral supplementation reduced negative psychotic and manic symptoms among psychosis patients, with no serious adverse events (3 human). No PEA changes emerged in either preclinical psychosis model (2 animal) studied.DiscussionEvidence supports PEA signaling as a potential psychosis biomarker, also indicating a therapeutic role of its supplementation in the disorder.Systematic review registrationhttps://doi.org/10.17605/OSF.IO/AFMTK.

show abstract

“…Instead, studies of PEA in other neuropsychiatric disorders are still in their infancy, despite results seem promising. For instance, very recent clinical trials provided initial evidence that PEA may be a valid adjunctive treatment in acute mania ( 61 ) and schizophrenia ( 62 ). It is worth mentioning that, while not being the focus of this review, results presented here support a potential role of PEA also in depressive-like symptoms ( 20 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence

et al. 2022

View full text Add to dashboard Cite

Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogenous attempt to contrast such neurodegeneration-related pathophysiological mechanisms, restore homeostatic balance, and prevent further damage. Among these naturally occurring molecules, palmitoylethanolamide (PEA) has been independently associated with neuroprotective and anti-inflammatory properties, raising interest into the possibility that its supplementation might represent a novel therapeutic approach in supporting the body-own regulation of many pathophysiological processes potentially contributing to neurocognitive disorders. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in neurocognitive disorders, finding 33 eligible outputs. Studies conducted in animal models of neurodegeneration indicate that PEA improves neurobehavioral functions, including memory and learning, by reducing oxidative stress and pro-inflammatory and astrocyte marker expression as well as rebalancing glutamatergic transmission. PEA was found to promote neurogenesis, especially in the hippocampus, neuronal viability and survival, and microtubule-associated protein 2 and brain-derived neurotrophic factor expression, while inhibiting mast cell infiltration/degranulation and astrocyte activation. It also demonstrated to mitigate β-amyloid-induced astrogliosis, by modulating lipid peroxidation, protein nytrosylation, inducible nitric oxide synthase induction, reactive oxygen species production, caspase3 activation, amyloidogenesis, and tau protein hyperphosphorylation. Such effects were related to PEA ability to indirectly activate cannabinoid receptors and modulate proliferator-activated receptor-α (PPAR-α) activity. Importantly, preclinical evidence suggests that PEA may act as a disease-modifying-drug in the early stage of a neurocognitive disorder, while its protective effect in the frank disorder may be less relevant. Limited human research suggests that PEA supplementation reduces fatigue and cognitive impairment, the latter being also meta-analytically confirmed in 3 eligible studies. PEA improved global executive function, working memory, language deficits, daily living activities, possibly by modulating cortical oscillatory activity and GABAergic transmission. There is currently no established cure for neurocognitive disorders but only treatments to temporarily reduce symptom severity. In the search for compounds able to protect against the pathophysiological mechanisms leading to neurocognitive disorders, PEA may represent a valid therapeutic option to prevent neurodegeneration and support endogenous repair processes against disease progression.

show abstract

Adjuvant palmitoylethanolamide therapy with risperidone improves negative symptoms in patients with schizophrenia: A randomized, double-blinded, placebo-controlled trial

Cited by 16 publications

References 62 publications

Comprehensive evaluation of 45 augmentation drugs for schizophrenia: a network meta-analysis

Comprehensive evaluation of 45 augmentation drugs for schizophrenia: a network meta-analysis

Questioning the role of palmitoylethanolamide in psychosis: a systematic review of clinical and preclinical evidence

Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence

Contact Info

Product

Resources

About