psiquiatria-nutricional-guu-2019

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Letter to the Editor / Reply
depression are generally small, and consequently, only the “big 
pharma” are willing and able to afford expensive randomized con-
trolled trials (RCTs) with the highest standard methodology in or-
der to successfully detect the small effect, while the “non-patent-
able” treatments without financial incentives fail to attract suffi-
cient resources and the RCTs with inconsistent quality might thus 
be associated with inconsistent results [10]. This is indeed an area 
where not only more replication of high-quality studies with larger 
sample size and longer duration are needed, but also better identi-
fication of the high-risk populations who would be benefited from 
n-3 PUFAs is waiting for elucidation. To optimize patients’ care 
under the best human knowledge, practice guidelines from credible 
scientific societies addressing safe and promising pharmacological 
and non-pharmacological therapies (e.g., nutrition, exercise, mind-
fulness, and other lifestyle interventions) are as much needed. 
Therefore, the opinion leaders have responsibilities to provide 
guidance on the less-touched areas by drug trials.
We read with great interest the letter by Thesing et al. [1] and 
are delighted to see their comments stating that (1) the guideline 
[2] helps to bring clarity and (2) the cautioning about the recom-
mendation of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as 
prophylactic treatment in high-risk populations.
Given this is the first guideline in nutritional psychiatry based on 
current evidence and experts’ consensus, we strove to be conservative 
but still provide room for clinical practicality without overemphasiz-
ing the efficacy in areas with less solid evidence, including prophylac-
tic use. In this regard, the tone of this item is obviously different from 
the other items with higher level and more consistent evidence, that 
is, we recommended that clinicians “could consider the potential” use 
in high-risk populations. Furthermore, we want to highlight the need 
in selection and characterization of these populations. Consider 
interferon-α-induced depression in patients with chronic hepatitis C 
viral infection as an example [3]: not all the patients receiving 
interferon-α developed depressive disorders; however, patients who 
developed depression commonly experienced recurrence afterwards 
[4]. Previous studies had also shown that baseline n-3 PUFA levels 
and certain genetic variations may assist in predicting the onset, 
symptomatology, and illness courses of depression in this specific 
population [5–7]. These findings should therefore not be taken as ab-
solute direction, yet they could be helpful for clinicians, patients, and 
their family when facing uncertainties in similar clinical situations.
Despite extensive supportive evidence from epidemiological 
survey, as well as case-controlled association studies measuring n-3 
PUFA blood concentrations [8], the clinical trials and meta-analy-
ses revealed inconsistent results of n-3 PUFAs’ therapeutic and pro-
phylactic effects in depression mainly because of common method-
ological flaws [9], which are rarely found in high-quality clinical 
drug trials conducted by large pharmaceutical companies [10]. The 
therapeutic effects of one single treatment for complex diseases like 
Received: October 17, 2019
Accepted: October 18, 2019
Published online: November 19, 2019
© 2019 S. Karger AG, Basel
www.karger.com/pps
Psychother Psychosom
Reply to the Letter to the Editor: Response to 
“International Society for Nutritional Psychiatry 
Research Practice Guidelines for Omega-3 Fatty 
Acids in the Treatment of Major Depressive 
Disorder” by Guu et al. (2019)
Ta-Wei Guu a, b Kuan-Pin Su a, c 
a
 Departments of Psychiatry and Mind-Body Interface Laboratory 
(MBI-Lab), China Medical University Hospital, Taichung, Taiwan; 
b
 Division of Psychiatry, Departments of Internal Medicine, China 
Medical University Beigang Hospital, Yunlin, Taiwan; c College of 
Medicine, China Medical University, Taichung, Taiwan
Prof. Kuan-Pin Su
Department of Psychiatry
China Medical University Hospital
No. 2, Yuh-Der Road, Taichung 404 (Taiwan)
E-Mail cobolsu @ gmail.com
DOI: 10.1159/000504232
References
 1 Thesing CS, Lamers F, Bot M, et al. Response to “International Society for 
Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Ac-
ids in the Treatment of Major Depressive Disorder” by Guu et al. (2019). 
Psychother Psychosom 2019, DOI:10.1159/000504100.
 2 Guu TW, Mischoulon D, Sarris J, Hibbeln J, McNamara RK, Hamazaki 
K, et al. International Society for Nutritional Psychiatry Research Prac-
tice Guidelines for Omega-3 Fatty Acids in the Treatment of Major De-
pressive Disorder. Psychother Psychosom. 2019; 88(5): 263–73.
 3 Su KP, Lai HC, Yang HT, Su WP, Peng CY, Chang JP, et al. Omega-3 fatty 
acids in the prevention of interferon-alpha-induced depression: results from 
a randomized, controlled trial. Biol Psychiatry. 2014 Oct; 76(7): 559–66.
 4 Chiu WC, Su YP, Su KP, Chen PC. Recurrence of depressive disorders after 
interferon-induced depression. Transl Psychiatry. 2017 Feb; 7(2):e1026.
 5 Su KP, Lai HC, Peng CY, Su WP, Chang JP, Pariante CM. Interferon-
alpha-induced depression: comparisons between early- and late-onset 
subgroups and with patients with major depressive disorder. Brain Behav 
Immun. 2019 Aug; 80: 512–8.
 6 Su KP, Huang SY, Peng CY, Lai HC, Huang CL, Chen YC, et al. Phos-
pholipase A2 and cyclooxygenase 2 genes influence the risk of interferon-
alpha-induced depression by regulating polyunsaturated fatty acids lev-
els. Biol Psychiatry. 2010 Mar; 67(6): 550–7.
 7 Chang JP, Lai HC, Yang HT, Su WP, Peng CY, Gałecki P, et al. Polyun-
saturated fatty acids levels and initial presentation of somatic symptoms 
induced by interferon-alpha therapy in patients with chronic hepatitis C 
viral infection. Nutr Neurosci. 2017 Jun; 20(5): 291–6.
 8 Lin PY, Huang SY, Su KP. A meta-analytic review of polyunsaturated 
fatty acid compositions in patients with depression. Biol Psychiatry. 2010 
Jul; 68(2): 140–7.
 9 Lin PY, Mischoulon D, Freeman MP, Matsuoka Y, Hibbeln J, Belmaker 
RH, et al. Are omega-3 fatty acids antidepressants or just mood-improv-
ing agents? The effect depends upon diagnosis, supplement preparation, 
and severity of depression. Mol Psychiatry. 2012 Dec; 17(12): 1161–3.
10 Su KP. Are we all the same? The critical role of translational brain, behavior, 
and immunity research in East Asia. Brain Behav Immun. 2019 Nov; 82: 1–2.
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