L-Arginine Add-On Treatment for Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

Abstract

ÖZETAmaç: Şizofrenide mevcut ilaç tedavileri kısmen etkili olduğundan güçlendirme veya kombinasyon tedavileri sık olarak uygulanmaktadır. Nitrik oksitin (NO) şizofreninin fizyopatolojisinde rol oynadığı öne sürülmektedir. L-arjinin NO öncülü olan bir esansiyel aminoasittir. Bu çalışmada şizofreni veya şizoafektif bozukluk tanısı konmuş klinik belirtileri kısmen devam eden hastaların mevcut tedavilerine eklenen L-arjinin'in, şizofreninin pozitif, negatif ve depresif belirtileri üzerindeki etkisinin incelemesi amaçlanmıştır.Yöntem: Çalışmaya 12 şizofreni veya şizoafektif bozukluk tanısı konmuş hasta dahil edilmiştir. Hastaların mevcut tedavilerine günde iki kez 3 g L-arjinin rastgele, çift kör, plasebo kontrollü ve çapraz geçişli şekilde eklenmiştir. Üç haftalık tedavi döneminin ardından 7 günlük ilaçsız dö-nem ve daha sonra ikinci 3 haftalık tedavi dönemine geçilmiştir. Current drug treatments for schizophrenia are only partially effective and combination/augmentation strategies are commonly used. Nitric Oxide (NO) may play a role in the pathophysiology of schizophrenia. L-arginine is the precursor of NO. In this study, we aimed to investigate whether L-arginine add-on to current medication might improve positive, negative, and depressive symptoms in schizophrenia/ schizoaffective disorder patients in partial remission. Method:The study was designed as a randomized, double-blind, placebo-controlled, crossover study of L-arginine 3 g b.i.d. as an add-on treatment to the patients' usual medication. Twelve patients diagnosed with schizophrenia/schizoaffective disorder were included. The duration of the treatment was 3 weeks, with a wash-out period of 7 days before alternation for the second arm. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS), and the Clinical Global Impression (CGI) scales. Results: Our analyses revealed that L-arginine 6 g/day add-on to usual treatment was not superior to placebo for positive, negative, and depressive symptoms associated with schizophrenia as assessed with PANSS, CDSS and CGI scales. Conclusion:In our study, L-arginine did not seem to have an effect on schizophrenia symptoms. Studies with a larger sample size, with higher doses of L-arginine, and with a longer duration are needed for a definite conclusion.

The Nitric Oxide (NO) Donor Sodium Nitroprusside (SNP) and Its Potential for the Schizophrenia Therapy: Lights and Shadows

“…Conversely, SNP was unable to express an antipsychotic profile in clinical trials in which patients were older, cigarette smokers, presenting less serious negative symptoms and with longer disease course respect to the studies in which the efficacy of SNP was revealed [ 60 , 61 , 62 , 63 ]. The role of nicotine as a critical factor of the ineffectiveness of SNP should also be considered since it interferes with NO and reduces SNP efficacy [ 64 ]. It can be thus hypothesized that SNP seem to improve schizophrenia symptoms when is administered in young patients, no smokers and having a short history of the disease.…”

“…There is scant evidence concerning the clinical efficacy of other NO modulators in schizophrenia and the results reported are contradictory. Specifically, in randomized, double-blind, placebo-controlled studies either the NO precursor L-arginine (repeatedly administered in patients under medication) [ 64 ] or the NO donor glyceryl trinitrate (GTN) (chronically administered in first-episode unmedicated patients) [ 65 ] failed to improve schizophrenia symptoms. Both studies were conducted in a small size of participants and only one dose of compound was used.…”

Amino acids and acylcarnitines as potential metabolomic markers of schizophrenia: new approaches to diagnostics and therapy

“…Âûÿâëÿåìûå èçìåíåíèÿ â àìèíîêèñëîòíîì ñïåêòðå ñîçäàþò ïðåäïîñûëêè äëÿ ðàçâèòèÿ íîâûõ ïåðñïåêòèâíûõ òåðàïåâòè÷åñêèõ ñòðàòåãèé â ïëàíå ïðèìåíåíèÿ â òåðàïèè ïñèõè÷åñêèõ ðàññòðîéñòâ àìèíîêèñëîò èëè ïðåïàðàòîâ, âîçäåéñòâóþùèõ íà èõ ìåòàáîëèçì [54][55][56][57][58][59][60].…”

BPC 157, L-NAME, L-Arginine, NO-Relation, in the Suited Rat Ketamine Models Resembling “Negative-Like” Symptoms of Schizophrenia

“…Importantly, this triple application, L-NAME vs. L-arginine vs. combination [ 8 ], would markedly overwhelm the regular level in the corresponding NO-studies, the application of the one single NO-agent (i.e., L-NAME) (i.e., for review, see [ 4 ]). Evidently, as demonstrated with the “positive-like” schizophrenia models’ symptoms [ 8 ], the triple application would better define the whole NO-system complexity (otherwise, the successful use of either NOS-blocker [ 12 , 29 , 30 ] or L-arginine [ 31 , 32 ] might disable each other value in the schizophrenia therapy [ 12 , 29 , 30 , 31 , 32 ]). This might be the case despite the fact that the neurobiology of the positive symptoms (i.e., mesolimbic pathways that involve dopamine and glutamate networks) is distinct from that of negative symptoms (i.e., fronto-cortical temporal and cortico-striatal pathways) [ 4 , 5 ].…”