Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Association between Serum Lipids and Antipsychotic Response in Schizophrenia

Author(s): David D. Kim, Alasdair M. Barr, Diane H. Fredrikson, William G. Honer and Ric M. Procyshyn*

Volume 17, Issue 9, 2019

Page: [852 - 860] Pages: 9

DOI: 10.2174/1570159X17666190228113348

Price: $65

Abstract

Metabolic abnormalities are serious health problems in individuals with schizophrenia. Paradoxically, studies have noted an association where individuals who gained body weight or who have increased their serum lipids demonstrated a better antipsychotic response. As serum lipids serve as more specific physiological markers than body weight, the objective of this study was to review studies that examined the association between changes in serum lipids and changes in symptoms during antipsychotic treatment in individuals with schizophrenia. A Medline® literature search was performed. Fourteen studies were included and analyzed. Evidence suggests that increases in serum lipids may be associated with decreases in symptoms during antipsychotic treatment. This inverse association may be independent of confounding variables, such as weight gain, and may be most evident during treatment with clozapine. Also, according to recent randomized controlled trials, lipid-lowering agents do not appear to worsen symptoms although this needs to be further investigated in clozapine-treated patients. Future studies should investigate the association in question in a larger population and identify underlying mechanisms.

Keywords: Serum lipids, triglycerides, cholesterol, dyslipidemia, antipsychotics, treatment response, clozapine, schizophrenia.

Graphical Abstract
[1]
D.E., Hert M.; Schreurs, V.; Vancampfort, D.; Van Winkel, R. Metabolic syndrome in people with schizophrenia: A review. World Psychiatry, 2009, 8(1), 15-22.
[http://dx.doi.org/10.1002/j.2051-5545.2009.tb00199.x] [PMID: 19293950]
[2]
Olfson, M.; Gerhard, T.; Huang, C.; Crystal, S.; Stroup, T.S. Premature Mortality among adults with schizophrenia in the United States. JAMA Psychiatry, 2015, 72(12), 1172-1181.
[http://dx.doi.org/10.1001/jamapsychiatry.2015.1737] [PMID: 26509694]
[3]
Nasrallah, H.A. A typical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol. Psychiatry, 2008, 13(1), 27-35.
[http://dx.doi.org/10.1038/sj.mp.4002066] [PMID: 17848919]
[4]
Correll, C.U.; Manu, P.; Olshanskiy, V.; Napolitano, B.; Kane, J.M.; Malhotra, A.K. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA, 2009, 302(16), 1765-1773.
[http://dx.doi.org/10.1001/jama.2009.1549] [PMID: 19861668]
[5]
Cai, H.L.; Tan, Q.Y.; Jiang, P.; Dang, R.L.; Xue, Y.; Tang, M.M.; Xu, P.; Deng, Y.; Li, H.D.; Yao, J.K. A potential mechanism underlying atypical antipsychotics-induced lipid disturbances. Transl. Psychiatry, 2015, 5, e661.
[http://dx.doi.org/10.1038/tp.2015.161] [PMID: 26485545]
[6]
Misiak, B.; Stańczykiewicz, B.; Łaczmański, Ł.; Frydecka, D. Lipid profile disturbances in antipsychotic-naive patients with first-episode non-affective psychosis: A systematic review and meta-analysis. Schizophr. Res., 2017, 190, 18-27.
[http://dx.doi.org/10.1016/j.schres.2017.03.031] [PMID: 28325572]
[7]
Raben, A.T.; Marshe, V.S.; Chintoh, A.; Gorbovskaya, I.; Müller, D.J.; Hahn, M.K. The complex relationship between antipsychotic-induced weight gain and therapeutic benefits: A systematic review and implications for treatment. Front. Neurosci., 2018, 11, 741.
[http://dx.doi.org/10.3389/fnins.2017.00741] [PMID: 29403343]
[8]
Procyshyn, R.M.; Wasan, K.M.; Thornton, A.E.; Barr, A.M.; Chen, E.Y.; Pomarol-Clotet, E.; Stip, E.; Williams, R.; Macewan, G.W.; Birmingham, C.L.; Honer, W.G. Changes in serum lipids, independent of weight, are associated with changes in symptoms during long-term clozapine treatment. J. Psychiatry Neurosci., 2007, 32(5), 331-338.
[PMID: 17823649]
[9]
Pande, S.; Procyshyn, R.M.; Nazerali, M.; Attwood, D.; Chow, K. Do triglycerides modulate the effectiveness of clozapine? Int. Clin. Psychopharmacol., 2002, 17(4), 197-199.
[http://dx.doi.org/10.1097/00004850-200207000-00007] [PMID: 12131604]
[10]
Procyshyn, R.M.; Honer, W.G.; Barr, A.M. Do serum lipids predict response to clozapine treatment? J. Psychiatry Neurosci., 2009, 34(2), 168.
[PMID: 19270766]
[11]
Garyfallos, G.; Dimelis, D.; Kouniakis, P.; Sidiropoulos, N.; Karastergiou, A.; Lavrentiadis, G.; Giouzepas, J.; Fokas, K. Olanzapine versus risperidone: weight gain and elevation of serum triglyceride levels. Eur. Psychiatry, 2003, 18(6), 320-321.
[http://dx.doi.org/10.1016/j.eurpsy.2003.06.002] [PMID: 14611929]
[12]
Atmaca, M.; Kuloglu, M.; Tezcan, E.; Ustundag, B. Serum leptin and triglyceride levels in patients on treatment with a typical antipsychotics. J. Clin. Psychiatry, 2003, 64(5), 598-604.
[http://dx.doi.org/10.4088/JCP.v64n0516] [PMID: 12755665]
[13]
Huang, T.L.; Chen, J.F. Serum lipid profiles and schizophrenia: effects of conventional or atypical antipsychotic drugs in Taiwan. Schizophr. Res., 2005, 80(1), 55-59.
[http://dx.doi.org/10.1016/j.schres.2005.05.001] [PMID: 15964176]
[14]
Hermes, E.; Nasrallah, H.; Davis, V.; Meyer, J.; McEvoy, J.; Goff, D.; Davis, S.; Stroup, T.S.; Swartz, M.; Lieberman, J.; Rosenheck, R. The association between weight change and symptom reduction in the CATIE schizophrenia trial. Schizophr. Res., 2011, 128(1-3), 166-170.
[http://dx.doi.org/10.1016/j.schres.2011.01.022] [PMID: 21334853]
[15]
Lally, J.; Gallagher, A.; Bainbridge, E.; Avalos, G.; Ahmed, M.; McDonald, C. Increases in triglyceride levels are associated with clinical response to clozapine treatment. J. Psychopharmacol. (Oxford), 2013, 27(4), 401-403.
[http://dx.doi.org/10.1177/0269881112472568] [PMID: 23325369]
[16]
Terevnikov, V.; Stenberg, J.H.; Tiihonen, J.; Chukhin, E.; Joffe, M.; Burkin, M.; Joffe, G. Relationships between pharmacotherapy-induced metabolic changes and improved psychopathology in schizophrenia: data from a mirtazapine and first-generation antipsychotics combination trial. Int. J. Neuropsychopharmacol., 2013, 16(7), 1661-1666.
[http://dx.doi.org/10.1017/S146114571200137X] [PMID: 23217660]
[17]
Chen, S.F.; Hu, T.M.; Lan, T.H.; Chiu, H.J.; Sheen, L.Y.; Loh, E.W. Severity of psychosis syndrome and change of metabolic abnormality in chronic schizophrenia patients: severe negative syndrome may be related to a distinct lipid pathophysiology. Eur. Psychiatry, 2014, 29(3), 167-171.
[http://dx.doi.org/10.1016/j.eurpsy.2013.04.003] [PMID: 23769679]
[18]
Sharma, E.; Venkatasubramanian, G.; Varambally, S.; Sivakumar, P.T.; Subbakrishna, D.K.; Gangadhar, B.N. Antipsychotic induced metabolic changes & treatment response: a prospective study. Asian J. Psychiatr., 2014, 11, 39-44.
[http://dx.doi.org/10.1016/j.ajp.2014.05.001] [PMID: 25453695]
[19]
Chukhin, E.; Terevnikov, V.; Takala, P.; Hakko, H.; Putkonen, H.; Räsänen, P.; Stenberg, J.H.; Eronen, M.; Joffe, G. Is there an interrelationship between the effects of antipsychotics on psychopathology and on metabolism? Nord. J. Psychiatry, 2016, 70(3), 190-194.
[http://dx.doi.org/10.3109/08039488.2015.1074283] [PMID: 26450657]
[20]
Solberg, D.K.; Bentsen, H.; Refsum, H.; Andreassen, O.A. Lipid profiles in schizophrenia associated with clinical traits: a five year follow-up study. BMC Psychiatry, 2016, 16, 299.
[http://dx.doi.org/10.1186/s12888-016-1006-3] [PMID: 27562545]
[21]
Gjerde, P.B.; Dieset, I.; Simonsen, C.; Hoseth, E.Z.; Iversen, T.; Lagerberg, T.V.; Lyngstad, S.H.; Mørch, R.H.; Skrede, S.; Andreassen, O.A.; Melle, I.; Steen, V.M. Increase in serum HDL level is associated with less negative symptoms after one year of antipsychotic treatment in first-episode psychosis Schizophr. Res, 2017. S0920-9964(17), 30670-9.
[22]
Luckhoff, H.; Phahladira, L.; Scheffler, F.; Asmal, L.; du Plessis, S.; Chiliza, B.; Kilian, S.; Emsley, R. Weight gain and metabolic change as predictors of symptom improvement in first-episode schizophrenia spectrum disorder patients treated over 12 months Schizophr. Res., 2018. S0920-9964(18), 30682
[http://dx.doi.org/10.1016/j.schres.2018.11.031]
[23]
Mascitelli, L.; Pezzetta, F.; Goldstein, M.R. Is statin use safe in individuals with psychotic disorders? J. Clin. Psychiatry, 2008, 69(9), 1499.
[http://dx.doi.org/10.4088/JCP.v69n0919a] [PMID: 19193350]
[24]
Chaudhry, I.B.; Husain, N.; Drake, R.; Dunn, G.; Husain, M.O.; Kazmi, A.; Hamirani, M.M.; Rahman, R.; Stirling, J.; Deakin, W. Add-on clinical effects of simvastatin and ondansetron in patients with schizophrenia stabilized on antipsychotic treatment: pilot study. Ther. Adv. Psychopharmacol., 2014, 4(3), 110-116.
[http://dx.doi.org/10.1177/2045125313511487] [PMID: 25057343]
[25]
Deakin, W.; Husain, N.; Parker, A.J.J.; Husain, M.O.; Kazmi, A.; Rahman, Ru.; Hamirani, M.M.; Kiran, T.; Mehmood, N.; Dunn, G.; Drake, R.; Chaudhry, I.B. Efficacy of ondansetron and simvastatin on cognition and negative symptoms in established schizophrenia. Neuropsychopharmacology, 2014, 39, S355-S356.
[26]
Ghanizadeh, A.; Rezaee, Z.; Dehbozorgi, S.; Berk, M.; Akhondzadeh, S. Lovastatin for the adjunctive treatment of schizophrenia: a preliminary randomized double-blind placebo-controlled trial. Psychiatry Res., 2014, 219(3), 431-435.
[http://dx.doi.org/10.1016/j.psychres.2014.06.039] [PMID: 25017614]
[27]
Vincenzi, B.; Stock, S.; Borba, C.P.; Cleary, S.M.; Oppenheim, C.E.; Petruzzi, L.J.; Fan, X.; Copeland, P.M.; Freudenreich, O.; Cather, C.; Henderson, D.C. A randomized placebo-controlled pilot study of pravastatin as an adjunctive therapy in schizophrenia patients: effect on inflammation, psychopathology, cognition and lipid metabolism. Schizophr. Res., 2014, 159(2-3), 395-403.
[http://dx.doi.org/10.1016/j.schres.2014.08.021] [PMID: 25261882]
[28]
Sayyah, M.; Boostani, H.; Ashrafpoori, M.; Pakseresht, S. Effects of atorvastatin on negative sign in chronic schizophrenia: A double blind clinical t rial. Iran. J. Pharm. Res., 2015, 14(4), 1269-1274.
[PMID: 26664396]
[29]
Tajik-Esmaeeli, S.; Moazen-Zadeh, E.; Abbasi, N.; Shariat, S.V.; Rezaei, F.; Salehi, B.; Akhondzadeh, S. Simvastatin adjunct therapy for negative symptoms of schizophrenia: a randomized double-blind placebo-controlled trial. Int. Clin. Psychopharmacol., 2017, 32(2), 87-94.
[http://dx.doi.org/10.1097/YIC.0000000000000159] [PMID: 27941358]
[30]
Bu, D.X.; Griffin, G.; Lichtman, A.H. Mechanisms for the anti-inflammatory effects of statins. Curr. Opin. Lipidol., 2011, 22(3), 165-170.
[http://dx.doi.org/10.1097/MOL.0b013e3283453e41] [PMID: 21412153]
[31]
Meyer, U.; Schwarz, M.J.; Müller, N. Inflammatory processes in schizophrenia: a promising neuroimmunological target for the treatment of negative/cognitive symptoms and beyond. Pharmacol. Ther., 2011, 132(1), 96-110.
[http://dx.doi.org/10.1016/j.pharmthera.2011.06.003] [PMID: 21704074]
[32]
Shen, H.; Li, R.; Yan, R.; Zhou, X.; Feng, X.; Zhao, M.; Xiao, H. Adjunctive therapy with statins in schizophrenia patients: A meta-analysis and implications. Psychiatry Res., 2018, 262, 84-93.
[http://dx.doi.org/10.1016/j.psychres.2018.02.018] [PMID: 29427912]
[33]
Kim, D.D.; Barr, A.M.; Thornton, A.E.; Honer, W.G.; Procyshyn, R.M. Statin add-on therapy for schizophrenia: Is the effect the same for clozapine? Psychiatry Res., 2018, 263, 289-290.
[http://dx.doi.org/10.1016/j.psychres.2018.02.039] [PMID: 29566972]
[34]
Petersen, A.M.; Pedersen, B.K. The anti-inflammatory effect of exercise. J. Appl. Physiol. (1985), 2005, 98(4), 1154-1160
[35]
Mann, S.; Beedie, C.; Jimenez, A. Differential effects of aerobic exercise, resistance training and combined exercise modalities on cholesterol and the lipid profile: review, synthesis and recommendations. Sports Med., 2014, 44(2), 211-221.
[http://dx.doi.org/10.1007/s40279-013-0110-5] [PMID: 24174305]
[36]
Firth, J.; Cotter, J.; Elliott, R.; French, P.; Yung, A.R. A systematic review and meta-analysis of exercise interventions in schizophrenia patients. Psychol. Med., 2015, 45(7), 1343-1361.
[http://dx.doi.org/10.1017/S0033291714003110] [PMID: 25650668]
[37]
Scheewe, T.W.; Backx, F.J.; Takken, T.; Jörg, F.; van Strater, A.C.; Kroes, A.G.; Kahn, R.S.; Cahn, W. Exercise therapy improves mental and physical health in schizophrenia: a randomised controlled trial. Acta Psychiatr. Scand., 2013, 127(6), 464-473.
[http://dx.doi.org/10.1111/acps.12029] [PMID: 23106093]
[38]
Poulin, M.J.; Chaput, J.P.; Simard, V.; Vincent, P.; Bernier, J.; Gauthier, Y.; Lanctôt, G.; Saindon, J.; Vincent, A.; Gagnon, S.; Tremblay, A. Management of antipsychotic-induced weight gain: prospective naturalistic study of the effectiveness of a supervised exercise programme. Aust. N. Z. J. Psychiatry, 2007, 41(12), 980-989.
[http://dx.doi.org/10.1080/00048670701689428] [PMID: 17999270]
[39]
Kim, D.D.; Lang, D.J.; Warburton, D.E.; Barr, A.M.; Smith, G.N.; Thornton, A.E.; White, R.F.; Honer, W.G.; Procyshyn, R.M. Effects of exercise on serum triglycerides and symptoms of schizophrenia. J. Clin. Psychopharmacol., 2017, 37(2), 273-274.
[http://dx.doi.org/10.1097/JCP.0000000000000648] [PMID: 28225749]
[40]
Procyshyn, R.M.; Kennedy, N.B.; Marriage, S.; Wasan, K.M. Plasma protein and lipoprotein distribution of clozapine. Am. J. Psychiatry, 2001, 158(6), 949-951.
[http://dx.doi.org/10.1176/appi.ajp.158.6.949] [PMID: 11384905]
[41]
Yamamoto, H.; Takada, T.; Yamanashi, Y.; Ogura, M.; Masuo, Y.; Harada-Shiba, M.; Suzuki, H. VLDL/LDL acts as a drug carrier and regulates the transport and metabolism of drugs in the body. Sci. Rep., 2017, 7(1), 633.
[http://dx.doi.org/10.1038/s41598-017-00685-9] [PMID: 28377633]
[42]
Dehouck, B.; Fenart, L.; Dehouck, M.P.; Pierce, A.; Torpier, G.; Cecchelli, R. A new function for the LDL receptor: Transcytosis of LDL across the blood-brain barrier. J. Cell Biol., 1997, 138(4), 877-889.
[http://dx.doi.org/10.1083/jcb.138.4.877] [PMID: 9265653]
[43]
Tse, L.; Procyshyn, R.M.; Fredrikson, D.H.; Boyda, H.N.; Honer, W.G.; Barr, A.M. Pharmacological treatment of antipsychotic-induced dyslipidemia and hypertension. Int. Clin. Psychopharmacol., 2014, 29(3), 125-137.
[http://dx.doi.org/10.1097/YIC.0000000000000014] [PMID: 24169026]
[44]
Whitney, Z.; Procyshyn, R.M.; Fredrikson, D.H.; Barr, A.M. Treatment of clozapine-associated weight gain: a systematic review. Eur. J. Clin. Pharmacol., 2015, 71(4), 389-401.
[http://dx.doi.org/10.1007/s00228-015-1807-1] [PMID: 25627831]
[45]
Fredrikson, D.H.; Boyda, H.N.; Tse, L.; Whitney, Z.; Pattison, M.A.; Ott, F.J.; Hansen, L.; Barr, A.M. Improving metabolic and cardiovascular health at an early psychosis intervention program in Vancouver, Canada. Front. Psychiatry, 2014, 5, 105.
[46]
Lang, D.J.; Barr, A.M.; Procyshyn, R.M. Management of medication-related cardiometabolic risk in patients with severe mental Illness. Curr. Cardiovasc. Risk Rep., 2013, 7(4), 283-287.
[http://dx.doi.org/10.1007/s12170-013-0321-1] [PMID: 23864926]
[47]
Yuen, J.W.Y.; Kim, D.D.; Procyshyn, R.M.; White, R.F.; Honer, W.G.; Barr, A.M. Clozapine-induced cardiovascular side Effects and autonomic dysfunction: A systematic review. Front. Neurosci., 2018, 12, 203.
[http://dx.doi.org/10.3389/fnins.2018.00203]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy