Study of Antidepressants in Parkinson’s disease or SAD-PD, a first-of-its-kind study published today in the medical journal Neurology, has found that two common antidepressants ease depression in people with Parkinson’s disease (PD) without aggravating motor symptoms. The drugs tested in the study, led by Michael J. Fox Foundation (MJFF) Scientific Advisory Board member Irene Hegeman Richard, MD, of the University of Rochester, were paroxetine (brand name Paxil) and venlafaxine extended release (brand name Effexor XR).
Richard’s team, which included investigators from 20 different university sites throughout North America, performed a three-month double-blind, placebo-controlled clinical trial for depression, funded by the National Institutes of Health. They found that those taking either drug experienced a significantly greater improvement in symptoms related to depression versus those taking a placebo pill.
MJFF spoke with Richard and with Maurizio Facheris, MD, MSc, associate director of research programs at MJFF to gauge what the study results could mean for people living with PD and depression.
NOTE: The medical information contained in this article is for general information purposes only. The Michael J. Fox Foundation has a policy of refraining from advocating, endorsing or promoting any drug therapy, course of treatment, or specific company or institution. It is crucial that care and treatment decisions related to Parkinson’s disease and any other medical condition be made in consultation with a physician or other qualified medical professional.
MJFF: Let’s begin with the basics: Why a study on depression in Parkinson’s? Is treating depression in people with PD different than treating other forms of depression?
IR: PD is associated with changes in brain chemistry and patients with PD may be on a number of other medications that affect brain function. For these reasons, there were concerns that antidepressant medications may not work the same as they do in someone who does not have PD.
MJFF: What causes depression in PD?
IR: In general, we do not think that depression in PD is simply a reaction to having a chronic neurological condition. We believe that it may be due to the underlying changes in brain chemistry and circuitry from the disease itself. Evidence for this includes the fact that depression sometimes starts before patients even develop motor symptoms.
MF: Most antidepressants focus on serotonin, one of the brain’s neurotransmitters. If dopamine is like the motor oil to keep the body’s systems controlling movement running smoothly, then serotonin is like the motor oil for a person’s mood. The brain’s serotonin and dopaminergic systems are closely related, and so when a person’s dopamine level goes down (the primary cause of the motor symptoms of PD), so too does his or her level of serotonin. Therefore it is not at all surprising that people with PD might experience depression.
MJFF: Tell us about the study’s findings.
IR: This is the largest clinical trial evaluating antidepressant medications in Parkinson’s disease to date. Many physicians, including myself, have long prescribed antidepressants for those with PD, but there have always been questions about their efficacy and possible side effects, including the potential to make motor symptoms worse. This study seems to begin to put these questions to rest.
We tested antidepressants from two different classes of drugs: Paroxetine is a selective serotonin reuptake inhibitor (SSRI) and venlafaxine is a serotonin and norepinephrine reuptake inhibitor (SNRI). We found that both were significantly more effective than a placebo pill in treating depression, as measured by the Hamilton Rating Scale for Depression, a tool used by clinicians to detect the presence and severity of symptoms of clinical depression. Those taking paroxetine showed a 59 percent improvement on the scale; venlafaxine a 52 percent improvement; placebo only 32 percent.
The other really good news from the study was that on the whole, medications were well tolerated and participants didn’t experience worsening of their motor symptoms from taking the drugs.
MJFF: How have physicians treated depression in people with PD to date?
IR: Physicians have used a variety of antidepressant medications to treat depression in PD. But prior to this study, there was little evidence on which to base decisions. Tricyclic antidepressants (TCAs) are an older class of drugs that are effective in people with PD, but that have a lot of side effects. SSRIs, which were the next class of available antidepressant drugs, were considered to be effective and better tolerated than TCAs in the general population. A few studies of SSRIs involving people with PD had been done in the past, but questions remained regarding their effectiveness. There were also concerns that they might worsen motor symptoms.
The newest class of antidepressants, the SNRIs (which, like the older TCAs affect both norepinephrine and serotonin) have been shown to be effective and well tolerated in depressed patients who don’t have PD but they had never been studied in patients with PD. So we included one SSRI medication and one SNRI medication in the study. Again, the study found that both were more effective than placebo and were generally well tolerated. The study wasn’t, however, designed to compare the drugs against each other.
MJFF: What are next research steps that might follow from the SAD-PD results?
IR: This study says to the community that ‘we already have medications available to treat depression in people with PD, and we can use them.’ We should be more confident prescribing these drugs moving forward.
But we hope to learn more, in particular, about those people in the study who did not respond to the medications tested. How can we predict who will respond to antidepressants, and what can we do for these patients? We didn’t test this in SAD-PD.
MF: It’s always useful for clinicians to have real study results to refer to. SAD-PD confirms two drugs that are useful in PD. Future studies could focus on other antidepressants that doctors might prescribe.
MJFF: For those who might be depressed, what would you recommend that they do?
IR: Unfortunately, many people are reluctant to admit that they are depressed since there can be a stigma attached to depression. Some people even view it as a sign of weakness and something that they can ‘get over.’ It is important to realize that depression is a part of the disease and isn’t something that one can ‘will away.’ I firmly believe that seeking out treatment is a sign of strength: People who acknowledge that they are suffering from depression and proactively look to do something about this should be commended. They will likely experience significant relief when their depression is treated.
MF: It’s important to seek out help to reverse the often vicious circle of depression. When you feel blue, you are less likely to go out, and this can be seriously detrimental to people with PD if it prevents them from staying socially connected or from exercising to help improve their motor symptoms.
If you are experiencing depression, speak openly about it with your neurologist. Depression can manifest itself in a variety of ways that may not always be obvious to you, such as loss of appetite, difficulty sleeping, fatigue, irritability, and/or anxiety. Caregivers are also good at helping to identify changes that might be taking place that you may not notice in yourself; if your spouse or other close connection mentions changes in your mood or personality, take it seriously. Depression can be deadly when it goes untreated.