| Abstract | Repetitivna transkranijska magnetska stimulacija (rTMS) neinvazivna je tehnika stimulacije mozga koja je učinkovita u liječenju velikoga depresivnoga poremećaja (VDP-a). Prevalencija depresije veća je kod žena nego kod muškaraca. Razlike između spolova u farmakoterapijskom antidepresivnom učinku teško je generalizirati. Uočena je vjerojatna povezanost kratkotrajnih
učinaka rTMS-a sa spolom, ali u većini studija učinak spola nije bio zasebno analiziran, pa nije bilo moguće donijeti konkluzivne zaključke. Cilj je ovog istraživanja ispitati spolne razlike u učinkovitosti terapije VDP-a rTMS-om upotrebom zavojnice oblika osmice. Proveli smo industrijski neovisnu, unicentričnu, randomiziranu, kontroliranu, jednostruko zaslijepljenu studiju od svibnja 2020. do listopada 2020. u Psihijatrijskoj bolnici "Sveti Ivan", Zagreb, Hrvatska. Pacijenti su randomizirani u dvije skupine: jednu liječenu rTMS-om sa zavojnicom oblika osmice i standardnom farmakoterapijom (47 pacijenata) i drugu liječenu
samo standardnom farmakoterapijom (43 pacijenta). Koristili smo stratificiranu (za dob, spol i težinu depresije) blok randomizaciju sa slučajnom veličinom blokova od 4, 6 i 8 sudionica i sudionika. Primarni ishod bila je promjena na Hamiltonovoj ljestvici ocjene depresije-17 (HAM-D17) nakon četiri tjedna liječenja. Varijable čiji smo mogući zbunjujući učinak kontrolirali multivarijabilnom statističkom analizom bile su dob, dob početka VDP-a, dijagnoza, liječenje SIPPS-om, SIPPSN-om i ostalim antidepresivima. Nakon prilagodbe za planirane zbunjujuće varijable snižavanje rezultata HAM-D17 bilo je statistički značajno više u skupini liječenoj rTMS-om + standardnom farmakoterapijom nego u kontrolnoj skupini liječenoj samo standardnom farmakoterapijom. Kod žena je snižavanje rezultata HAM-D17 tijekom četiri tjedna liječenja bilo statistički značajno i klinički relevantno veće u pokusnoj skupini liječenoj rTMS-om i standardnom farmakoterapijom nego u kontrolnoj skupini liječenoj samo standardnom farmakoterapijom. Interakcija ispitivane skupine, dakle liječenje rTMS-om i standardnom farmakoterapijom ili samo standardnom farmakoterapijom i spola na promjenu rezultata HAM-D17 od uključivanja do nakon četiri tjedna liječenja nije bila
statistički značajna nakon prilagodbe na varijable s mogućim zbunjujućim učinkom. Nije moguće prihvatljivo pouzdano tvrditi kako između muškaraca i žena postoje razlike u učinku rTMS-a pomoću zavojnice oblika osmice, ali rezultati ukazuju na potrebu za daljnjim istraživanjima. |
| Abstract (english) | Introduction
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that is effective in treatment of major depressive disorder (MDD). The prevalence of depression is higher in women than in men. It has been observed that women respond better to selective serotonin reuptake inhibitors (SSRIs) than men, but not all studies confirm these findings, so it is difficult to generalize gender differences in pharmacotherapeutic antidepressant effect. A probable association of short-term antidepressant properties of rTMS with gender has been observed. Meta-analysis published in 2019. showed that rTMS MDD studies with higher proportion of women participants observed a higher response rates at 3rd and 6th months, but since the gender-related effects were not specifically analyzed it was not possible to draw conclusive conclusions. Men respond more strongly to placebo treatment but the placebo (sham) response to repetitive transcranial magnetic stimulation (rTMS) in MDD is not associated with gender.
Objective
To investigate gender differences in the efficacy of 8-coil rTMS on major depressive disorder (MDD).
Methods
We performed an industry-independent, unicentric, randomized, controlled, single-blinded study from May 2020 to October 2020 in Psychiatric Hospital "Sveti Ivan", Zagreb, Croatia. Patients were randomized into two groups: one treated with 8-coil rTMS and standard pharmacotherapy (47 patients) and the other treated with the standard pharmacotherapy alone
(43 patients). We used a stratified (for age, gender and depression severity), permuted blocks randomization with the randomized block sizes of 4, 6 and 8 participants. The primary outcome was Hamilton Depression Rating Scale-17 (HDRS). Variables whose possible confounding effect we controlled by multivariable statistical analysis were: age, diagnosis, duration of illness, treatment with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and other antidepressants.
Results
After the adjustment for all preplanned possible confounding variables, the lowering of HAMD17 score after 4-weeks treatment was statistically significantly different between patients treated with 8-coil rTMS + standard pharmacotherapy, and patients treated with standard pharmacotherapy alone. In women, the lowering of HAM-D17 score over four weeks of
treatment was statistically significantly and clinically relevantly larger in the experimental group treated with rTMS and standard pharmacotherapy than in the control group treated with standard pharmacotherapy alone (F (1, 26) = 7.49; p = 0.011; ω2 = 0.08; false discovery rate; FDR <10%). This could not be reliably claimed for men. The interaction of the study group, i.e. treatment with rTMS and standard pharmacotherapy or standard pharmacotherapy alone, and gender on the change in HAM-D17 scores from enrolment to after four weeks of treatment was not statistically significant after adjustment for age, age at MDD onset, diagnosis, treatment with SSRIs, SNRIs and other antidepressants (F (1, 74) = 2.05; p = 0.157; ω2 = 0.14).
Conclusion
It cannot be reasonably reliably claimed that there are differences in the effect of rTMS between men and women using the 8-coil, but the results indicate the need for further research. |
