Another unique aspect of agomelatine is the evidence that it can improve sleep quality. This is a very ideal effect because people with depression often encounter sleep disorders. From a clinical point of view, the ability of this drug to reintroduce circadian rhythms may be unique to most other antidepressants. It often interferes with the sleep cycle, Dr. Trevor Norman said
Although agomelatine has a high affinity for MT1 and MT2 receptors and 5HT2B and 5HT2C receptors, it has a low affinity for several other receptors, such as adrenergic receptors, ion channels, and dopaminergic, GABAergic, muscarinic, histamine, benzodiazepine, and σ recipient. In addition, it has little effect on monoamine oxidase and neurotransmitter transport molecules. The agonistic effect of the drug on the melatonin receptor and the antagonistic effect on the serotonin receptor is very important to achieving the antidepressant effect.
Agomelatine has also been shown to increase brain-derived neurotrophic factor mRNA and protein levels in the hippocampus. This effect is related to increased neurogenesis, which may produce an antidepressant effect.
Superior efficacy alone is not enough to make antidepressants perform well in ruthless clinical practice, said John Donohue, director of British medical mental health, which provides services and education to maximize the benefits of mental health drugs. Acceptability is at least as important, or even more important. Considering the efficacy and tolerance, agomelatine is superior to other drugs. In fact, the efficacy and tolerance of agomelatine have been proved to be one of the three preferred drugs for the treatment of depression after 8 weeks. The other two drugs are serotonin reuptake inhibitors Etaplam and vortioxetine.
In a recent online meta-analysis, agomelatine was found to have the highest acceptance of 21 antidepressants. This may suggest that agomelatine may be a suitable first-line treatment for depression because it has the same efficacy but better tolerance compared with most antidepressants. However, Dr. Norman has a different view: my impression is that not many psychiatrists in clinical practice will wholeheartedly agree to an assessment based on their own personal experience with drugs. He believes that agomelatine is more appropriate as a second-line treatment.
Like most antidepressants, agomelatine appears to be effective for a wide range of depression, rather than specific types of depression. It has shown therapeutic effects on monophasic depression and depression with certain diseases such as Parkinson's disease, type 2 diabetes, and cardiovascular disease. one
Agomelatine has been evaluated in bipolar depression based on its regulatory effect on circadian rhythm; However, it has not proved to be of significant benefit to this situation. Dr. Norman explained: Most antidepressants can 'transition' patients from depression to hypomania/mania. The conversion rate is between 20% and 40%, and some drugs are more likely to do this than others. Most clinical guidelines recommend the use of antidepressants and mood stabilizers to treat bipolar disorder or no antidepressants at all. Obviously, this will depend on the disease of the individual patient's history. There is evidence that the conversion rate of agomelatine is lower than that of most antidepressants.
Agomelatine has been approved in Europe and Australia. However, its development in the United States has stopped because phase 3 trials showed negative results and there is evidence that the drug can cause hepatotoxicity. It was also suggested that the current evaluation scale used to evaluate depression could not accurately represent the circadian rhythm effect of agomelatine in depression, resulting in inconsistent clinical results. one
According to Dr. Norman, agomelatine is likely to be used as a second-line treatment for depression, at least in Australia. The situation in Australia may be artificial because although the drug has been approved by the therapeutic supplies authority (Australian drug regulator), it is not in the drug benefit plan. In Australia, the drugs in the drug benefit plan are subsidized by the government through our universal health care system Medicare, he said. Not all drugs are automatically included. Agomelatine is one of the drugs not included. This means that patients who take drugs need to pay out of their own pocket. In the course of treatment, the cost may be high, so general practitioners are unlikely to prescribe agomelatine to many patients.
In addition to cost concerns, other limitations of current agomelatine treatment include hepatotoxicity, lack of longitudinal studies, and limited evidence of its benefits for older people with depression. Some guidelines have been introduced to monitor liver function before, during, and after treatment with agomelatine to address issues related to hepatotoxicity. A new clinical evaluation method of depression is also needed to accurately monitor the impact of depression and agomelatine on all aspects of the disease, including sleep patterns.
Despite these limitations, Donoghue believes that agomelatine may be a very useful treatment option for many patients, partly because of its very low burden of side effects and partly because it is beneficial to sleep. In fact, although agomelatine has not been accepted worldwide for the treatment of depression, its unique characteristics have aroused new interest in the pharmaceutical and medical community, especially in view of the increasing need to develop new treatment strategies for depression resistant to traditional treatment.