Q: What is depression and how common is it?
A: Depression is a common mental disorder with symptoms such as anxiety, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, low energy, and poor concentration. These problems can become chronic or recurrent and can lead to substantial impairments in an individual’s ability to function on a daily basis. Depression is very common, affecting about 45 million people in the US alone, and is among the leading causes of disability worldwide.(1) There are several forms of depressive disorders; the most common is major depressive disorder (MDD).(2) In general, MDD patients may need pharmacotherapy, and those who suffer from the severe form of MDD appear to be the most responsive to this type of therapy. Rexahn is developing Serdaxin®, a potential next generation treatment for depression, which goes beyond conventional therapy, targeting serotonin, dopamine, and neuronal survival and enabling a multi-pronged approach to treating depression.
Q: What causes depression?
A: There is no single known cause of depression. Rather, it likely results from a combination of genetic, biochemical, environmental, and psychological factors. Brain-imaging technologies, such as magnetic resonance imaging, have shown that the brains of patients with depression look different than those without depression. The parts of the brain responsible for regulating mood, thinking, sleep, appetite, and behavior appear to function abnormally in patients with depression. In addition, important neurotransmitters such as serotonin, dopamine, and norepinephrine appear to be out of balance.(2) Serdaxin®, in particular, tackles the serotonin- or dopamine-regulated mechanisms.
Q: How is depression treated?
A: Once diagnosed, a person with depression has a number of treatment options. The most common treatments are medication and psychotherapy. Anti-depressant drugs work to normalize naturally occurring neurotransmitters in the brain, notably serotonin, dopamine, and norepinephrine. Scientists studying depression have found that these neurotrasmitters are involved in regulating mood. Currently, the most widely-prescribed types of antidepressant medications are called selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). These antidepressants are more popular than the older classes of antidepressants (e.g. MAOI and tricyclics), largely because they have relatively fewer side effects.(2) Still, there remain significant unmet needs for better and safer therapies. Rexahn believes that a drug like Serdaxin®, with the ability to enhance both serotonin and dopamine, may be able to provide greater efficacy, fewer side effects, and potentially reduce relapse compared to currently available therapies.
Q: What are the drawbacks of existing anti-depressants?
A: Although SSRIs and SNRIs have become norms in current depression treatment, these drugs have substantial drawbacks. According to Dr. Fava of Harvard University, more than 50% of SSRI or SNRI-treated patients fail to respond to these anti-depressants. In addition, up to 50% of patients who responded to SSRI or SNRIs are reported to experience relapse. These anti-depressants can also cause a variety of undesirable side effects, including nausea, weight gain, insomnia, and sexual dysfunction, as noted on these drug labels. These side effects may affect compliance in up to 30% of patients. Because of the limited efficacy and unwanted side-effects, there remains a significant opportunity for safer and more effective anti-depressant drugs.(3-5) Serdaxin® has a well-established human safety profile, and in a Phase IIa study of the drug in patients with MDD, Serdaxin® demonstrated proof of concept in this patient population.
Q: How does Serdaxin® meet unmet medical needs?
A: Unlike current SSRI/SNRI anti-depressants, Serdaxin® works as a dual enhancer of serotonin and dopamine levels in the brain. Serdaxin® enhances these neurotransmitters by a mechanism different from the SSRI/SNRI anti-depressants. As a dual enhancer of serotonin and dopamine, Serdaxin® may provide additional benefits for patients suffering from depression characterized by negative mood states, the loss of positive mood states, or the mixture of both. This new approach is expected to enable Serdaxin® to treat a subset of patients who are prone to relapse and unresponsive to conventional treatments.
Q: What is the clinical profile of Serdaxin®?
A: The results of a recently completed proof-of-concept, randomized, double-blind, placebo-controlled, dose-exploring clinical trial of Serdaxin® indicate that it may be effective in treating patients with severe MDD. In the study, patients with severe MDD had a significant response to 5mg of Serdaxin® (response rate minus placebo effect = 35.7%) and experienced remission (remission rate minus that of placebo effect = 28.6%). Furthermore, the 5mg Serdaxin®-treated group reported 40% less adverse effects than the placebo group.
Based on pre-clinical studies, Serdaxin® may have an inverted, U-shape dose-response curve. This inverted, dose-response relationship may explain the observation of, “the lower the dosage, the better the efficacy,” in the Phase IIa trial. Due to this phenomenon, higher doses of Serdaxin® may not be effective, suggesting an additional benefit with respect to the risk of overdose problems prevalent in other psychogenic medications.
Q: What are other potential indications of Serdaxin®?
A: Because of Serdaxin®’s neuroprotective potential in animals treated with neurotoxins, in addition to its anti-depressant activity, Rexahn believes that the drug may have important applications in the treatment of human neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer disease (AD). Because more than 60% of patients with PD or AD also suffer from depression, Serdaxin®’s potential anti-depressant and neuroprotective activities may offer an ideal therapy for these neurological diseases. Moreover, animal model studies suggest that Serdaxin® reduces aggressive behavior and relieves anxiety.
1. http://www.who.int/mental_health/management/depression/definition/en/index.html
2. http://www.nimh.nih.gov/health/publications/depression/complete-index.shtml#pub1
3. M. Fava, J. Clin. Psych., 61, Suppl. 1, 26, (2000)
4. E. Dailly, F. Chenu, C.E. Renard, M. Bourin, Fundam. Clin. Pharmacol. 18, 601 (2004)
5. J.M. Azorin, P.M. Llorca, N. Despiegel, P. Verpillat, Encephale. 30, 158 (2004)
