The Committee for Treatment Guidelines of Mood Disorders, Japanese Society of Mood Disorders, published a Japanese guideline for the treatment of late‐life depression in 2020. Based on that guideline, the present guideline was developed and revised to incorporate the suggestions of global experts and the latest published evidence. In the diagnosis of late‐life depression, it is important to carefully differentiate it from bipolar disorders, depressive states caused by physical and organic brain disease, drug effects, and dementia, and to determine the comorbidity between late‐life depression and dementia. It is necessary to fully understand the clinical characteristics and psychosocial background of late‐life depression, evaluate the patient's condition, and provide basic interventions based on these factors. Problem‐solving therapy, reminiscence therapy/life review therapy, and behavioral activation therapy, and other forms of psychotherapy can reduce depressive symptoms. In terms of pharmacotherapy, newer antidepressants or non‐tricyclic antidepressants are recommended for late‐life depression, and it is recommended that the efficacy of least the minimal effective dosage should first be determined. Switching antidepressants and aripiprazole augmentation can be used to treatment‐resistant therapy. Electroconvulsive therapy and repetitive transcranial magnetic stimulation have demonstrated usefulness for late‐life depression. Exercise therapy, high‐intensity light therapy, and diet therapy also show some effectiveness and are useful for late‐life depression. Continuation therapy should be maintained for at least 1 year after remission.

Several studies have proved that low-frequency transcranial magnetic stimulation (TMS) of the right dorsolateral prefrontal cortex (DLPFC) showed an antidepressant effect, although its mechanism is still not completely elucidated. The aim of the present study was to clarify the alteration in neuroanatomical function elicited by low-frequency TMS of the right DLPFC in treatment-resistant depression and to detect the difference between responders and nonresponders to TMS. Single-photon emission computed tomography with ^99mTc-ethyl cysteinate dimer was performed in 14 right-handed male patients with treatment-resistant unipolar depression before and after low-frequency TMS of the right DLPFC. Five 60-second 1-Hz trains were applied and 12 treatment sessions were administered within a 3-week period (total pulses, 3,600). The Hamilton Rating Scale for Depression was administered and the regional cerebral blood flow (rCBF) was analyzed using statistical parametric mapping (SPM2). After TMS treatment in 14 patients, the score on the Hamilton Rating Scale for Depression decreased significantly, and considerable decreases in rCBF were seen in the bilateral prefrontal, orbitofrontal, anterior insula, right subgenual cingulate, and left parietal cortex, but no significant increase in rCBF occurred. Additionally, as compared with 8 nonresponders, 6 responders showed significant increases in rCBF at baseline in the left hemisphere including the prefrontal and limbic-paralimbic regions. These results suggest that the antidepressant effect of low-frequency TMS of the right DLPFC is associated with a decrease in rCBF in the limbic-paralimbic regions via the ipsilateral subgenual cingulate, and increased rCBF at baseline in the left hemisphere may be involved in the response to low-frequency TMS treatment.

Aims: Low-frequency transcranial magnetic stimulation (TMS) to the right prefrontal cortex has been shown to be effective in treatment-resistant depression. The aim of the present study was to investigate changes in regional cerebral blood flow (rCBF) after low-frequency right prefrontal stimulation (LFRS), and neuroanatomical correlates of therapeutic efficacy of LFRS in treatment-resistant depression.Methods: Twenty-six patients with treatmentresistant depression received five 60-s 1-Hz trains over the right prefrontal cortex, and 12 treatment sessions were administered during 3 weeks. Brain scans were acquired before and after LFRS using single photon emission computed tomography with 99m Tc-ethyl cysteinate dimer. Severity of depression was assessed on the Hamilton Depression Rating Scale (HDRS).Results: Significant decreases in rCBF after LFRS were seen in the prefrontal cortex, orbitofrontal cortex, subgenual cingulate cortex, globus pallidus, thalamus, anterior and posterior insula, and midbrain in the right hemisphere. Therapeutic efficacy of LFRS was correlated with decreases in rCBF in the right prefrontal cortex, bilateral orbitofrontal cortex, right subgenual cingulate cortex, right putamen, and right anterior insula. Conclusion:The antidepressant effects of LFRS in treatment-resistant depression may be associated with decreases in rCBF in the orbitofrontal cortex and the subgenual cingulate cortex via the right prefrontal cortex.

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