Depression drug market and research and development trends

Depression drug market and research and development trends

November 23, 2016 Source: Pharmaceutical Economics

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About 350 million people worldwide suffer from depression, the first major cause of disability worldwide. In the United States, 9.1% of people suffer from depression. Worldwide, patients receiving depression are less than half of the actual number of patients, and in some countries even less than one-tenth.

In addition to the continuous depression in the mood, depression is accompanied by a series of physiological reactions, such as: irritability, mental inability to concentrate, memory loss, slow response, learning communication disorders, more severe depression accompanied by chest tightness, slow heartbeat Uncontrollable emotions, inability to perceive emotions, etc.

Drug treatment VS psychotherapy

In a review of depression by Belmaker and Agam (Belmaker, Agam, 2008), the causes of depression are attributed to: genetic, biochemical effects, and external environmental influences.

The occurrence of depression has an important genetic basis. Early quantitative behavioral studies have shown that genetic factors can explain the variation of 24% to 55% of depression. Family studies have found that the relative morbidity rate of relatives is much higher than that of the general population.

For external environmental factors, the author understands that people with depression tend to have pessimistic and negative explanations for different interpretations of the same thing.

Among the biochemical factors, there are serotonin (5-HT) hypothesis, norepinephrine (NE) hypothesis, dopamine (DA) hypothesis, acetylcholine (Ach) hypothesis, and r-aminobutyric acid (GABA) hypothesis. Simply put, the concentration of these substances in the human body affects the mental state of the person. Therefore, various compounds have been developed for each hypothesis to increase or inhibit the concentration of certain related compounds, thereby alleviating the physiological response of patients due to depression.

Therefore, the treatment of depression requires both medical treatment and psychotherapy.

Depressive medication is a related compound developed based on a series of hypotheses. The current 5-HT hypothesis is gaining more and more attention. The hypothesis is that 5-HT can directly or indirectly participate in the regulation of human mood, 5-HT levels are associated with depression, and 5-HT levels are associated with mania. Therefore, selective serotonin reuptake inhibitors (SSRIs) block the recovery of 5-HT and increase the content of 5-HT, which acts as an antidepressant. This class of drugs is the most frequently used category in the entire antidepressant medication. The commonly used antidepressant drugs in China and their representative drugs are shown in Table 1.

Domestic and international sales comparison

US antidepressants reached $6.785 billion in 2014. Total sales of depression and anxiety drugs accounted for more than 40% of the central nervous drug market, while depression and schizophrenia treatments accounted for more than 80% of the world's psychotropic drugs.

Since most of the drugs used in the treatment of depression in the United States are heavyweight drugs, these drugs are being hit by the expiration of patents, so the overall sales growth is slowing or declining. However, the amount of prescriptions has not decreased. From 2014 to 2015, the prescription for antidepressants has increased by nearly 10% in the United States.

In contrast, antidepressant medication is still a relatively niche area. The reason is that the concept of depression is low in China. Most people still think that the cause of depression is mainly due to the failure of self-conformity. On the other hand, even if it is diagnosed as depression, there are many people. There is resistance to drugs. Therefore, in China, although the development process of the country has accelerated, various social contradictions have become prominent, people's life pressure has increased, and the incidence of depression has continued to rise. However, the medication for depression still involves only a very small part of the population.

According to data from the South, the overall sales volume of antidepressant drugs in hospital samples in 2015 was only 5.57 billion yuan, an increase of 10.83% compared with 2014. The top ten varieties of sales are shown in Table 2.

It can be seen that the top ten varieties of antidepressant drugs account for more than 98% of the total market, and the top five varieties account for about 70%. In China, the main market for antidepressant drugs is the products of the SSRIs category.

Three considerations and future trends

For the later development of antidepressant drugs, the following three aspects are mainly considered:

1.Lexapro will become the “gold standard” in the field of antidepressants

Compared to other anti-depressant products, escitalopram has good efficacy and safety performance, so it will become the benchmark in this field.

Subsequent R&D products are likely to have a place in the future antidepressant market unless they exceed escitalopram in terms of efficacy, tolerability or safety, or are far lower in price than other SSRIs. Otherwise, the overall market for antidepressant medications will still be dominated by SSRIs and their generics.

2. Critical clinical trials are becoming more and more standardized

Clinical trials for antidepressant medications need to include a generally validated clinical efficacy endpoint, such as the Hamilton's Depression Scale or the Montgomery Depression Scale, after 8 weeks of dosing, to see the patient's score change from baseline.

Therefore, future clinical research trends may be directed toward refractory patients or in combination with other medications for depression.

3. Changing the current treatment model is still the direction of research and development

Although some existing clinical early projects have suffered a certain degree of frustration, the future research and development trend is still to change the existing treatment mode.

Currently, several early clinical programs have the potential to alter existing treatment models for depression, all of which are monoamine reuptake inhibitors. The usual practice is to develop glutamate receptor modulators and to use them in combination with monoamine reuptake inhibitors. These new mechanisms of action are reflected in some early clinical projects.

However, leading compounds developed for the corticotropin releasing factor receptor, vasopressin receptor, and neurokinin receptor have all suffered some failure. Now, the development line for depression has avoided the two targets of corticotropin releasing factor receptor and neurokinin receptor.

ALKS 5461 is a non-addictive κ-type opioid receptor antagonist for the treatment of refractory depression and has been highly anticipated, but neither of the clinical trials of Phase II reached the primary clinical endpoint until the third trial. FORWARD-5, the drug reached the corresponding clinical endpoint.

Therefore, future research and development should be directed at refractory patients with depression and the use of biomarkers to determine the patient's response to drugs.

For the development of China's anti-depressant drug market, the author believes that it is not the speed of introduction of new products. More opportunities should be based on the market expansion brought about by people's understanding of depression and changes in their perceptions.

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