The effectiveness of Transcranial Photobiomodulation therapy (tPBM) on reducing anxiety, depression, and opioid craving in patients undergoing methadone maintenance treatment: a double-blind, randomized, controlled trial

In this study, both groups consisted of 32 males (91.4%) and 3 females (8.6%). The mean age of patients in the intervention group was 37.97 ± 10.58 years, while it was 39.66 ± 9.94 years in the control group (P = 0.495). Table 1 illustrates that there were no significant differences in educational level, marital status, and occupation between the two groups (p>0.05). The mean methadone doses in the two groups were 20.30 ± 8.81 cc and 18.40 ± 7.72 cc, respectively, with no significant difference (P = 0.337). Additionally, the mean duration of methadone use in the intervention and control groups was 6.01 ± 4.20 years and 4.91 ± 3.62 years, respectively (P = 0.245). There were no significant differences between the groups in terms of a history of using other drugs, smoking, neurological and mental diseases, suicide attempts, or use of psychiatric medications (p>0.05).

Table 1 The baseline characteristics of patients in the LLLT and control groupDepression

The HAM-D, used to assess the severity of depression, consists of 17 items, with each item scored on a scale from 0 to 4. This scale was developed by Max Hamilton in 1960 and is widely used in clinical settings. The scale has demonstrated high reliability and validity across various populations [22].

Before the intervention, the mean HAM-D score in both groups was 19.64 ± 3.52 and 19.45 ± 3.11 respectively, indicating no significant difference between the two groups (P-value=0.709). However, after the intervention, the sham tPBMT group consistently displayed significantly higher HAM-D scores immediately, one month, and three months later (P-value=0.001). At the end of the first and third months, patients in the LLL group had lower depression scores than the control group compared to pre-treatment, with significant effect sizes of 3.79 and 3.75, respectively.

Assessment of depression severity one-month post-intervention revealed that in the sham tPBMT group, 33 individuals (34%) had no depression, while none in the tPBMT group were without depression. Mild depression was observed in 55 individuals (56.7%) in the sham tPBMT group and 17 individuals (23%) in the tPBMT group. Furthermore, moderate depression was present in 9 individuals (9.3%) in the control group and 33 individuals (44.6%) in the tPBMT group. Lastly, severe depression was found in 24 cases (32.4%) in the sham tPBMT group and none in the tPBMT group (P = 0.001). (Table 2, Figure 2)

Table 2 The score of depression, anxiety, and opioid craving of patients in the LLLT and control group before and after interventionFig. 2figure 2

The score of depression, anxiety, and opioid craving of patients in the LLLT and control group before and after intervention

Anxiety

For assessing anxiety, the Hamilton Anxiety Rating Scale (HAM-A) was used, which contains 14 items, with scores ranging from 0 to 56, where higher scores indicate greater anxiety. The HAM-A, developed by Max Hamilton in 1959, is a widely recognized tool for assessing anxiety severity in clinical settings. This scale also shows strong validity and reliability [23].

Before the intervention, the average HAM-A scores in both groups were 21.00±5.93 and 20.27±6.67, respectively, with no significant difference between the two groups (P-value = 0.451). However, after the intervention, the sham tPBMT group consistently showed significantly higher HAM-A scores immediately, one month, and three months later (P-value=0.001). At the end of the first and third months, patients in the LLL group had lower depression scores than the control group compared to pre-treatment, with significant effect sizes of 1.48 and 1.51, respectively.

Specifically, one month after the intervention, anxiety was absent in 3 individuals (3.1%) in the sham tPBMT group, while none were without anxiety in the tPMBT group. Mild anxiety was observed in 92 individuals (94.8%) in the sham tPBMT group and 33 individuals (44.6%) in the tPBMT group. Mild to moderate anxiety was reported in 2 individuals (2.1%) in the sham tPBMT group and 29 individuals (39.2%) in the tPBMT group. Finally, moderate to severe anxiety was found in 12 individuals (16.2%) in the sham tPBMT group and none in the Tpbmt group (P-value = 0.001). (Table 2, Figure 2)

Opioid craving scale

For evaluating opioid cravings, the Opioid Craving Scale (OCS) was utilized. The OCS consists of 15 items, with scores ranging from 0 to 60, with higher scores indicating more intense cravings. This scale is specifically designed for assessing cravings in individuals with opioid use disorder and has been widely validated in clinical studies [24].

Before the intervention, the mean OCS scores in both groups were 22.42 ± 3.50 and 22.76 ± 3.31, respectively, showing no significant difference (P-value =0.528). However, post-intervention, the sham tPBMT group consistently exhibited significantly higher OCS scores immediately, one month, and three months later (P-value=0.001). At the end of the intervention, first and third months, patients in the LLL group had lower depression scores than the control group compared to pre-treatment, with significant effect sizes of 2.40, 4.13, and 4.15, respectively. (Table 2, Figure 2).

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