QUESTION: My sister suffers from depression and she has been prescribed several different antidepressant medications. While she feels marginally improved, her doctor is about to start her on a new drug to see if she can do better. Why is it so hard for some patients to find the "right" antidepressant?
ANSWER: Only about one-third of depressed individuals experience what's called "sustained remission" within a few weeks or months after starting an antidepressant medication. The lucky one-third has no depressive symptoms and stays that way for an extended period of time.
The majority of patients, however, must try several different drugs before finding one that produces the best results. Some of them may feel improvement on a particular drug, but are unable to continue with the treatment because they can't tolerate the drug's side effects. As a result, they switch to another medication. And they may change again if the next drug doesn't work. They might end up taking a combination of different drugs to get the desired effect. And, unfortunately, a third of patients don't receive any meaningful benefit from antidepressant medications.
The reason why it's so hard to match a patient with the right drug arises from the fact that depression isn't just one ailment.
"It is many, many different disorders," says Dr. Ayal Schaffer, a psychiatrist and head of Mood and Anxiety Disorders at Sunnybrook Health Sciences Centre.
"There could be two people who have nothing in common in terms of their experiences or their symptoms," yet both patients would get the same diagnosis of depression, says Dr. Schaffer who is also an Associate Professor in the Department of Psychiatry at the University of Toronto.
One patient, he explains, could be very sad, sleeping all the time, guilt-ridden and feeling suicidal. The other may be very irritable, agitated and restless, not sleeping well and feeling very anxious about the future.
Furthermore, the underlying causes of their mental health problems could be very different.
Doctors must use their clinical judgment - and a bit of guesswork - when they are prescribing an antidepressant to a patient for the first time.
There are almost 40 different antidepressant drugs that act on one or more neurotransmitters - serotonin, norepinephrine and dopamine - which are the chemical-messenger systems in the brain.
Dr. Schaffer says patients are less likely to respond rapidly to treatment if they are also afflicted with other mental health problems, such as being prone to substance or alcohol abuse.
"Those sorts of things are negative prognosticators and suggest that an antidepressant, on its own, may not be enough and you probably need to do other things to address these other factors," he says.
The longer patients go without getting proper treatment can also hamper their recovery. "If someone has been depressed for years, many things will have changed in their lives," he notes. "Their view of themselves has changed, their self-esteem has been affected." Prolonged depression also takes a toll on personal relationships, as well as work or school life.
Given the complexity of this disorder, maybe we shouldn't be surprised that many patients fail to respond to the first course of treatment.
Even so, doctors and researchers think they will eventually be able to minimize the trial-and-error in drug selection.
Using high-tech brain imaging, blood tests, and reams of data from clinical trials, they are searching for patterns that will help predict which drugs are most likely to benefit individual patients.
Numerous studies are now underway.
"This [area of research] represents a promising development, made possible by sophisticated neuro-imaging and more economic ways to look at genome-wide associations," says Dr. Sidney Kennedy, a professor of psychiatry at the University of Toronto and lead of the Canadian Biomarker Integration Network for Depression program.
Essentially, Dr. Kennedy and his co-researchers hope to classify the different subtypes of major depression and identify the "biomarkers" associated with each one of them. This information should help doctors make a relatively fast and accurate diagnosis as well as guide treatment selection.
Of course, any findings will need to be confirmed by other studies. It will take some time before all this promising research leads to changes in the way patients are diagnosed and treated. What are patients supposed to do in the meantime?
Dr. Schaffer points out that 60 per cent of depressed people will get at least some positive response when they begin taking an antidepressant.
"If a patient has just gone through years of depression and feels 30 per cent better [after starting an antidepressant], I would say that's wonderful - and now how are we going to build on that?"
With more energy, the patients might be able to do things that will aid their own recovery and give them a sense of accomplishment.
"Once people start to do more, it has a very positive effect on their mood and on their self-esteem," he adds. Regular exercise and better nutrition can contribute to their sense of wellbeing. "It's not just about what the medication can do."
Psychotherapy might also benefit some patients, although limited public funding for this type of treatment can be an additional obstacle to recovery.
Dr. Schaffer readily acknowledges that it can be difficult to take the first steps on the path to improved mental health. "Depression is cruel because it affects people's ability to do the things they need to do to get out of their depression," he says.
"It is a long, frustrating road and I see my patients struggle through that process. We would love to know immediately what is going to be the right treatment. But, ultimately, the only choice they have is to keep going," says Dr. Schaffer.
"Eventually, most people do get better. They just have to keep trying and trust that, at the end of the day, there is going to be benefit from the treatments."
Co-authored by Paul Taylor, Personal Health Navigator at Sunnybrook.MORE ON HUFFPOST:
Do you have persistent feelings of sadness or hopelessness that have lingered for at least two weeks and occur throughout the day, every day or nearly every day? Are these feelings interfering with school or work, or your relationships? This is a key symptom of clinical depression. We all have negative thoughts from time to time, and it’s natural to be sad when there is a serious event in our lives, like a death. The difference with clinical depression is that the feelings stick around and interfere with your ability to live your life day to day.
Many people with depression find it difficult to get out of bed — and we're not just talking about hitting the snooze button. For some, getting up seems nearly impossible. They may also find themselves spending unusual amounts of time in bed throughout the day, or having trouble with normal activities because of fatigue.
As tired as you may be, if you’re depressed you might also have trouble sleeping. Marked changes in sleeping patterns, like insomnia or increased time spent sleeping, is another symptom of clinical depression.
Some people either gain or lose weight when they have clinical depression because of their change in appetite. For some, this means an increase in appetite and possibly weight gain as a result. Others lose their appetite and struggle to eat much at all. In either case, a significant change is worth investigating.
We all have times when we feel a bit more introverted than usual, but when people have clinical depression, they can lose the sense of pleasure they used to get from their favourite activities or from engaging with others. This isolation can make it harder for friends and loved ones to see the other symptoms of depression a person may be exhibiting, which makes it more difficult to know when a person needs help.
It’s more often thought of as a symptom of ADHD, but an inability to concentrate or hold focus on one’s activities can be a sign of clinical depression. Of course, if someone with clinical depression is also having trouble sleeping, not eating well or has lost interest in regular activities, this symptom can be amplified.
This is the most serious symptom of depression, says Dr. Joe Taravella, a psychologist and the supervisor of Rusk’s Pediatric Psychology Service at NYU-Langone Medical Center in New York. “When you’re severely depressed, suicidal thoughts can become so prominent, you begin to make a plan for ending your life, as you feel there are no other options.” If you are experiencing suicidal thoughts, seek help or tell a trusted person in your life and ask for help — call your doctor, call 911, or go to an emergency room. And never assume that a person who talks about suicide won’t do it. If someone tells you they are feeling suicidal or discusses plans to end their life, always take it seriously and get help.
“Many people don’t realize that low levels of chronic irritability and anger can mask an underlying depression,” Taravella says, “which can be undiagnosed and untreated for years.” A study released last year found that more than half of men and women who were experiencing a major depressive episode reported irritability as a symptom. Constant irritability is also a symptom of depression seen in teenagers and children, one that could be written off as normal growing pains or teenage behaviour.
Yes, depression can literally hurt. There is increasing recognition of the physical symptoms of depression, which include headaches, stomach pain, and back pain. One study found half of patients with depression from around the world reported unexplained physical symptoms. But because these physical symptoms are often vague or have no logical explanation, they can be missed as as symptom of depression.
For people with severe depression, basic tasks of self care can seem too overwhelming to undertake, Taravella says. As well, personal hygiene may seem unimportant if you are feeling hopeless or worthless. If someone in your life is showing a marked decrease in personal hygiene, don’t assume they are simply lazy.
Going along with trouble with concentration, people with clinical depression often have memory issues that can add to their difficulties in maintaining day-to-day activities. “As a result of these symptoms, they are more likely to become inattentive to their environment and prone to falls and injuries,” he adds. A 2013 study found that this could be because clinical depression impairs the process of “pattern separation,” which is the ability to distinguish between things and experiences that are similar.
Some people who show signs of depression engage in what Taravella refers to as “externalizing behaviours,” which include substance abuse and risk-taking activities. Men are more likely to do it, he says. These behaviours can be a sign of an underlying mental-health problem, particularly if they’re out of the ordinary for the individual.
“If you recognize symptoms of depression, take action and immediately seek professional help,” Taravella advises. There are valuable resources out there, he says, including psychotherapy and antidepressants. Many people also find some relief with meditation and exercise, often in conjunction with other treatments. It can be difficult to navigate the process of finding the right help, especially if you are having trouble just getting out of bed. Try talking to a trusted friend or family member who can help you research options and even call a therapist for you.
It can take time for depression treatments to start making a difference, which is frustrating when you've taken the difficult step of admitting you need help. But while you work on medication and/or therapy, there are things you can do. Be as active as you can, Taravella says, and try to see friends. “Create small goals for yourself each week but don’t put a lot of pressure on yourself,” he suggests. While it can take time for depression symptoms to begin to lift, it may be worth seeking different treatment options if you are not seeing any improvement after two months.
“The best way to help someone who is depressed is to be a constant source of support for them,” Taravella says. This can sometimes be difficult, however, because people with depression tend to isolate themselves despite your efforts to stay in touch and/or get involved. You may also be able to help someone by making a doctor’s appointment for them. It’s a simple task to request an appointment, but for someone who is severely depressed it can seem incredibly daunting.
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