Major depressive disorder is a serious mental disorder in which treatment with antidepressant medication is associated with incidence of adverse events, such as constipation, diarrhea, dry mouth, headache, insomnia, and sexual dysfunction (SDys). Escitalopram (ESC), an effective and safe selective serotonin reuptake inhibitor with good tolerability, was used in this study. In this study, we investigated the prospective effect of Pycnogenol (PYC), an antioxidant, anti-inflammatory, and vasodilator agent, on ESC-induced SDys.
This was a randomized, parallel, open-label study. Seventy-two outpatients of both genders with depression were randomized into two groups as follows: 37 patients from the ESC + PYC group took 50 mg of PYC per day for 4 months in ESC co-treatment, and 35 subjects from the ESC group took ESC only. Five patients dropped out and were excluded from the analysis. The participants were examined every month (visits 1–4).
ESC use led to improvement of depressive symptoms and severity scored by standardized psychiatric tests. PYC co-treatment resulted in attenuation of SDys beginning at 1 month of treatment and continuing for two consecutive months. Furthermore, an increase in heart rate in the PYC group was registered.
We propose that PYC-mediated SDys attenuation is based on its ability to improve endothelial functions by its antioxidant, anti-inflammatory, vasodilatory, and anticoagulant action. We assume that the action of PYC on heart rate is in accordance with the aforementioned vasodilatory action of PYC and consequent baroreflex-mediated heart rate response. PYC co-treatment reduced ESC-induced SDys and elevated heart rate.
Aoki H , Nagao J , Ueda T , Strong JM , Schonlau F , Yu-Jing S , Lu Y , Horie S : Clinical assessment of a supplement of Pycnogenol® and L-arginine in Japanese patients with mild to moderate erectile dysfunction. Phytother. Res. 26, 204–207 (2012)
Araghi-Niknam M , Hosseini S , Larson D , Rohdewald P , Watson RR : Pine bark extract reduces platelet aggregation. Integr. Med. 2, 73–77 (2000)
Ashton AK , Jamerson BD , L. Weinstein W , Wagoner C : Antidepressant-related adverse effects impacting treatment compliance: results of a patient survey. Curr. Ther. Res. 66, 96–106 (2005)
Bauer M , Monz BU , Montejo AL , Quail D , Dantchev N , Demyttenaere K , Garcia-Cebrian A , Grassi L , Perahia DG , Reed C , Tylee A : Prescribing patterns of antidepressants in Europe: results from the Factors Influencing Depression Endpoints Research (FINDER) study. Eur. Psychiatry 23, 66–73 (2008)
Belmaker RH , Agam G : Major depressive disorder. N. Engl. J. Med. 358, 55–68 (2008)
Cates M : Selecting antidepressant therapy for patients with major depression. Am. J. Pharm. Educ. 65, 190–194 (2001)
Cesarone MR , Belcaro G , Rohdewald P , Pellegrini L , Ledda A , Vinciguerra G , Ricci A , Ippolito E , Fano F , Dugall M , Cacchio M , Di Renzo A , Hosoi M , Stuard S , Corsi M : Improvement of signs and symptoms of chronic venous insufficiency and microangiopathy with Pycnogenol®: a prospective, controlled study. Phytomedicine 17, 835–839 (2010)
Clayton A , Kornstein S , Prakash A , Mallinckrodt C , Wohlreich M : Changes in sexual functioning associated with duloxetine, escitalopram, and placebo in the treatment of patients with major depressive disorder. J. Sex. Med. 4, 917–929 (2007)
Corona G , Ricca V , Bandini E , Mannucci E , Lotti F , Boddi V , Rastrelli G , Sforza A , Faravelli C , Forti G , Maggi M : Selective serotonin reuptake inhibitor-induced sexual dysfunction. J. Sex. Med. 6, 1259–1269 (2009)
D’Andrea G : Pycnogenol: a blend of procyanidins with multifaceted therapeutic applications? Fitoterapia 81, 724–736 (2010)
Drieling RL , Gardner CD , Ma J , Ahn DK , Stafford RS : No beneficial effects of pine bark extract on cardiovascular disease risk factors. Arch. Intern. Med. 170, 1541–1547 (2010)
D̆uračková Z , Trebatický B , Novotný V , Žitňanová I , Breza J : Lipid metabolism and erectile function improvement by pycnogenol®, extract from the bark of Pinus pinaster in patients suffering from erectile dysfunction – a pilot study. Nutr. Res. 23, 1189–1198 (2003)
Enseleit F , Sudano I , Periat D , Winnik S , Wolfrum M , Flammer AJ , Fröhlich GM , Kaiser P , Hirt A , Haile SR , Krasniqi N , Matter CM , Uhlenhut K , Högger P : Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Eur. Heart J. 33, 1589–1597 (2012)
Ferguson JM : SSRI antidepressant medications: adverse effects and tolerability. Prim. Care Companion J. Clin. Psychiatry 3, 22–27 (2001)
Grimm T , Chovanová Z , Muchová J , Sumegová K , Liptáková A , Duracková Z , Högger P : Inhibition of NF-κB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol). J. Inflamm. (Lond.) 3, 1 (2006)
Grimm T , Skrabala R , Chovanová Z , Muchová J , Sumegová K , Liptáková A , Durackova Z , Högger P : Single and multiple dose pharmacokinetics of maritime pine bark extract (Pycnogenol) after oral administration to healthy volunteers. BMC Clin. Pharmacol. 6, 4 (2006)
Hatzimouratidis K , Amar E , Eardley I , Giuliano F , Hatzichristou D , Montorsi F , Vardi Y , Wespes E , European Association of Urology : Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur. Urol. 57, 804–814 (2010)
Hausenblas HA , Saha D , Dubyak PJ , Anton SD : Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J. Integr. Med. 11, 377–383 (2013)
Higgins A , Nash M , Lynch AM : Antidepressant-associated sexual dysfunction: impact, effects, and treatment. Drug Healthc. Patient Saf. 2, 141–150 (2010)
Hosseini S , Lee J , Sepulveda RT , Rohdewald P , Watson RR : A randomized, double-blind, placebo-controlled, prospective, 16 week crossover study to determine the role of Pycnogenol in modifying blood pressure in mildly hypertensive patients. Nutr. Res. 21, 1251–1260 (2001)
Jankyova S , Hlavackova L , Kralova E , Slazneva J , Drobna V , Zuzik P , Drafi F , Mucaji P , Racanska E : The evaluation of efficacy of Pycnogenol® fractions on endothelial dysfunction. Acta Fac. Pharm. Univ. Comen. 60, 7–14 (2013)
Kennedy SH , Andersen HF , Lam RW : Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis. J. Psychiatry Neurosci. 31, 122–131 (2006)
Kennedy SH , Lam RW , McIntyre RS , Tourjman SV , Bhat V , Blier P , Hasnain M , Jollant F , Levitt AJ , MacQueen GM , McInerney SJ , McIntosh D , Milev RV , Müller DJ , Parikh SV , Pearson NL , Ravindran AV , Uher R , CANMAT Depression Work Group: Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder. Can. J. Psychiatry 61, 540–560 (2016)
Kobori Y , Suzuki K , Iwahata T , Shin T , Sadaoka Y , Sato R , Nishio K , Yagi H , Arai G , Soh S , Okada H , Strong JM , Rohdewald P : Improvement of seminal quality and sexual function of men with oligoasthenoteratozoospermia syndrome following supplementation with L-arginine and Pycnogenol®. Arch. Ital. Urol. Androl. 87, 190–193 (2015)
Lamm S , Schönlau F , Rohdewald P : Prelox® for improvement of erectile function: a review. Eur. Bull. Drug Res. 11, 29–37 (2003)
Ledda A , Belcaro G , Cesarone MR , Dugall M , Schönlau F : Investigation of a complex plant extract for mild to moderate erectile dysfunction in a randomized, double-blind, placebo-controlled, parallel-arm study. BJU Int. 106, 1030–1033 (2010)
Lewer D , O’Reilly C , Mojtabai R , Evans-Lacko S : Antidepressant use in 27 European countries: associations with sociodemographic, cultural and economic factors. Br. J. Psychiatry 207, 221–226 (2015)
Liu X , Wei J , Tan F , Zhou S , Würthwein G , Rohdewald P : Antidiabetic effect of Pycnogenol® French maritime pine bark extract in patients with diabetes type II. Life Sci. 75, 2505–2513 (2004)
Montgomery SA , Asberg M : A new depression scale designed to be sensitive to change. Br. J. Psychiatry 134, 382–389 (1979)
Mullen W , Edwards CA , Crozier A : Absorption, excretion and metabolite profiling of methyl-, glucuronyl-, glucosyl- and sulpho-conjugates of quercetin in human plasma and urine after ingestion of onions. Br. J. Nutr. 96, 107–116 (2006)
Mülek M , Seefried L , Genest F , Högger P : Distribution of constituents and metabolites of maritime pine bark extract (Pycnogenol®) into serum, blood cells, and synovial fluid of patients with severe osteoarthritis: a randomized controlled trial. Nutrients 9, 443 (2017)
Müller MJ , Himmerich H , Kienzle B , Szegedi A : Differentiating moderate and severe depression using the Montgomery–Åsberg Depression Rating Scale (MADRS). J. Affect. Disord. 77, 255–260 (2003)
Nishioka K , Hidaka T , Nakamura S , Umemura T , Jitsuiki D , Soga J , Goto C , Chayama K , Yoshizumi M , Higashi Y : Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens. Res. 30, 775–780 (2007)
Nocun M , Ulicna O , Muchova J , Durackova Z , Watala C : French maritime pine bark extract (Pycnogenol®) reduces thromboxane generation in blood from diabetic male rats. Biomed. Pharmacother. 62, 168–172 (2008)
Pandey KB , Rizvi SI : Plant polyphenols as dietary antioxidants in human health and disease. Oxid. Med. Cell Longev. 2, 270–278 (2009)
Park Y-M : Serum prolactin levels in patients with major depressive disorder receiving selective serotonin-reuptake inhibitor monotherapy for 3 months: a prospective study. Psychiatry Investig. 14, 368–371 (2017)
Perry AG , Potter PA , Ostendorf W (2014): Clinical Nursing Skills and Techniques (8th ed.). Mosby, St. Louis, MO
Schäfer A , Chovanová Z , Muchová J , Sumegová K , Liptáková A , Durackova Z , Högger P : Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol). Biomed. Pharmacother. 60, 5–9 (2006)
Schönthal AH : Adverse effects of concentrated green tea extracts. Mol. Nutr. Food Res. 55, 874–885 (2011)
Siasos G , Tousoulis D , Antoniades C , Stefanadi E , Stefanadis C : L-Arginine, the substrate for NO synthesis: an alternative treatment for premature atherosclerosis? Int. J. Cardiol. 116, 300–308 (2007)
Sivonová M , Waczulíková I , Kilanczyk E , Hrnciarová M , Bryszewska M , Klajnert B , Durackova Z : The effect of Pycnogenol on the erythrocyte membrane fluidity. Gen. Physiol. Biophys. 23, 39–51 (2004)
Stanislavov R , Nikolova V : Treatment of erectile dysfunction with pycnogenol and L-arginine. J. Sex. Marital. Ther. 29, 207–213 (2003)
Stanislavov R , Nikolova V , Rohdewald P : Improvement of erectile function with Prelox: a randomized, double-blind, placebo-controlled, crossover trial. Int. J. Impot. Res. 20, 173–180 (2008)
Taner G , Aydın S , Aytaç Z , Başaran AA , Başaran N : Assessment of the cytotoxic, genotoxic, and antigenotoxic potential of Pycnogenol® in in vitro mammalian cells. Food Chem. Toxicol. 61, 203–208 (2013)
Yagi H , Sato R , Nishio K , Arai G , Soh S , Okada H : Effects of a supplement combining Pycnogenol® and L-arginine aspartate on lower urinary dysfunction compared with saw palmetto extract. J. Tradit. Complement. Med. 7, 117–120 (2017)