Are Antidepressants Effective?
By Melissa Churly
Anchor Magazine
Deborah Serani always pictured herself as Eeyore, the despondent and downhearted donkey from Winnie the Pooh. “I was always just a sad sack,” says the Smithtown, New York resident. “And I didn’t even realize there was something wrong with me.”
Serani says that even as a child she was sad. It wasn’t until she had a major episode of depression while in college that she realized she had been feeling this way all her life. “I guess it was the fact that I had left the protective environment of home and the stress of school just really made me plummet into feeling very, very depressed. I had isolated myself, I wasn’t going to class, I was having panic attacks. I was just a mess.”
She dropped out of school for the semester and began psychotherapy. The therapy taught her a lot about her depression and gave her the tools she needed to get out of crisis. “But I just returned to the state I was in before the breakdown, which is what I thought was normal, and I stayed steady that way until I had my child some 20 years later.”
After a serious postpartum depression, Serani sought help again. This time she was prescribed antidepressants. “My psychiatrist prescribed me Prozac and within two weeks I was feeling so much better. Within two months, I was feeling better than I had ever felt before. I felt full and content and that’s when I realized that for 34 years I had been depressed.”
Today, Serani is still on antidepressants, but that hasn’t stopped her from being a successful psychologist and psychoanalyst who has her own private practice helping people with all forms of depression and mental illness. She believes in the effectiveness of antidepressants as she has seen first hand how successfully they can work.
Unraveling the placebo effect
But not everyone is as convinced. A few recent studies, including one published in the Journal of Affective Disorders (February, 2009), attributed 68 percent of the benefit from antidepressants to the placebo effect. In 2008, a similar paper appeared in PLoS Medicine (Public Library of Science) suggesting that widely used selective serotonin reuptake inhibitors (SSRIs), including Prozac, Paxil, and the serotonin-norepinephrine reuptake inhibitor (SNRI)Effexor offer no clinically significant benefit over placebos for patients with moderate or severe depression (SSRIs and SNRIs are antidepressants that affect serotonin levels in the brain).
According to Pierre Blier, MD, director of the Mood Disorders Research Unit at the University of Ottawa Institute of Mental Health Research, Ottawa, Ontario, a lot of these findings come from short-term studies and clinical trials that followed patients for only a few weeks. It generally takes about four to six weeks for patients on antidepressants to start to feel noticeably better and an additional six to nine months for these medications to have a lasting effect and to reduce the likelihood of relapse.
“When people are depressed, they need to be treated for months and sometimes years, so if you just look at the effectiveness of antidepressants over a couple of weeks you are getting a very narrow window on the disorder,” he says. “If I asked you to assess the effectiveness of an obesity treatment you’re not going to look at six weeks, you’re going to look at a couple of months or even a year. Even if the treatment makes a patient lose 10 pounds a week for six weeks that’s great, but if they put the 60 pounds back on in the next six months, the treatment is pretty useless. The same holds true for treating depression.”
Blier also attributes the placebo effect seen in many of the studies to the environment in which the study participants are placed. He points out that depressed patients who have been ill for weeks, months, even years―who haven’t been adequately cared for―are suddenly seen by a psychiatrist on a weekly basis, they have access to a research nurse, and they have a number they can call 24 hours a day to reach a psychiatrist if something goes wrong. If both the treatment group and the placebo group have access to these services, it “…has a big therapeutic effect. In such a setting, the placebo group is getting some kind of indirect treatment because of the support that the research team is providing,” says Blier. In other words, although it appears some patients on placebo improve as much as those in the treatment group, that result may be because of the supportive and nurturing environment that both groups are placed in. But this effect doesn’t last long, says Blier. “At the end of the study, those who continue on active medication for six months or more do really well; the effects of the antidepressant are very robust. In all of the recent papers reporting a controversial action of antidepressants there is not a single word about the long term effect of these drugs.”
Peter Kramer, MD, author and clinical professor of psychiatry and human behavior at Brown University, Providence, Rhode Island, agrees. “These medicines do have a pretty good track record. If the placebo effect were so strong we would see a lot more people responding to antidepressants. These placebo effects wash out over time and patients often become depressed again.”
Finding the right mix
Although antidepressants are effective in treating depression, some patients with certain types of depression may not respond as well to these medications, according to Jonathan Alpert, MD, an associate professor of psychiatry at Harvard Medical School in Boston.
An example of this can be seen in depressed patients who also suffer from anxiety. “Antidepressants appear to work quite effectively for all forms of unipolar depression such as major depressive disorder and dysthymia. But for certain forms of depression, like those that include severe anxiety, patients tend to not respond as well to the antidepressants compared to those without anxiety,” he says.
Bipolar depression is another form of depression where antidepressants aren’t as effective. In fact it can be dangerous to treat this form of depression with antidepressants alone as there is a significant risk of causing mania. “In just a matter of days, a patient can go from being deeply depressed to being extremely agitated and activated. We typically use a different class of medications called mood stabilizers or antipsychotics along with antidepressants to treat this disorder,” says Alpert.
For people with mild to moderate depression, antidepressant medications may not be the only solution according to Raymond Lam, MD, professor of psychiatry at the University of British Columbia, Vancouver, British Columbia. “Psychotherapy is as effective for treating mild depression as medications. In this case it’s kind of a preference whether people want to do therapy or take medication. They both seem to help.”
Antidepressants have come a long way since they were first discovered in the early 1950s. In terms of effectiveness, the medications have stayed the same, but Alpert argues the newer generation antidepressants are safer today.
“The older classes of antidepressants, although they are still occasionally used today, have very significant side effects and have a lot of interactions with other medications that are potentially dangerous, including effects on heart rhythms and blood pressure,” he says.
Weighing the pros and cons
Today’s antidepressants still have side effects, but they are generally more tolerable to patients. Common side effects include insomnia, weight gain or loss, nausea, diarrhea, constipation, decreased sex drive, and dry mouth.
“You just have to weigh the pros and cons of the medication and see if the side effects are something you can live with. With the medication I take I have increased sweating and weight gain. I say to myself "okay so {I gain weight}, yeah it’s not great but if I wasn’t on the medication I’d be thinner and not happy. I’d sooner choose happy and shapely than that,’” says Serani.
Over the last decade, Alpert says great progress has also been made in determining strategies for combining medications in order to increase the effectiveness of antidepressants. “Nowadays if somebody doesn’t respond to several antidepressants we’ll often consider combining antidepressants with other medications or other antidepressants. For example, the antipsychotic Abilify on its own does not treat depression, but when it’s combined with an antidepressant it was found that it boosts the effectiveness of the antidepressant,” he says.
A mixture of antidepressants and antipsychotic medications is what keeps Lynn Slater’s depression under control. “When I was just taking the antidepressant I still had some symptoms, so when they put me on the anti-psychotic it really took everything away,” says the 49-year-old Vancouver resident. Slater first became depressed as a child but it wasn’t until she was in college that she actually received any help. “For over 20 years I felt a lot of hopelessness, I remember a lot of deep despair, anxiety, and sleeplessness and as I got older things got worse.”
Blier and his Mood Disorders Research unit have also been investigating this form of treatment. “We’re treating depression now the way all physicians treat asthma. At the first episode people get at least two or three medications for asthma, well we’re doing the same thing for depression. We’re trying to change the standard of care so that patients don’t have to wait months or even years to feel better.”
Personalizing the process
Another area that is actively being researched to improve the effectiveness of antidepressants is finding ways to better predict how people respond to each medication. Even though there is a significant data set to show their overall effectiveness, doctors often don’t know which medications will be most tolerable and effective for specific patients. Each patient is different and responds to medications in a different way, so it’s typically a trial and error system.
“It’s called pharmacogenomics,” says Serani. “It’s where researchers study patients’ genes to predict how they might respond to drugs. It’s going to make it easier to select the right drug and the right quantity. It’s like long ago when they used to make glasses to either exaggerate or minimize [vision], then over time they got really good at it and now you can get an individual prescription that is tailored to your needs.” Scientists are still in the early stages of examining this type of ‘personalized medicine’ but it is a very active area of study right now. Although it will be many years before this technology is available it will contribute greatly to improving the quality of care for depressed patients and will be well worth the wait, says Serani.
Monitoring how a person is doing on a specific antidepressant is also a key component in improving the effectiveness of these medications says Kramer. “The key to pharmacology is a good working relationship between a doctor and a patient.” When starting a new medication regimen, it may be necessary for the doctor to see the patient every week or every couple of weeks so that the dose can be adjusted or the antidepressant changed to maximize the benefit and minimize the side effects. It’s also important for the patient to inform his psychiatrist of any discomfort, or if he feels the medication isn’t working. A relationship of trust between the patient and doctor is important to making this happen.
Having the support of her healthcare team is another aspect that contributed to Slater’s recovery. “I have been seeing my psychiatrist and my psychiatric nurse since 1986. Having those relationships for all these years has been really helpful. Although I don’t have to go and see them as often since I’m doing very well, just knowing that I can call them if I need any help is very important,” she says.
In order for antidepressants to really be effective, Blier says they have to be taken properly by patients.
“If antidepressants stay on the shelf, they can’t possibly work. Sometimes there are side effects that can cause the patient to stop taking them or maybe the dose needs to be adjusted to make it work better. Patients become discouraged by this, but I really recommend going back to your physician so it can be adjusted to make it more tolerable rather than just stopping the medication.”
The low compliance rate among patients may also be a reason antidepressants get a bad reputation says Lam. “Unfortunately, people stop the medications much too early because they are feeling better and they don’t feel like they need the medication anymore. Taking an antidepressant is kind of like taking an antibiotic. If you stop taking the antibiotic too early, even if you are feeling better, the infection can come back. It’s the same with depression.”
It’s also important to note that not everyone has to keep taking antidepressants forever.
“For people who have a single episode of depression that has lasted less than two years, typically we continue to treat them for another six to nine months after all of the depressive symptoms are gone. At that point we will attempt to taper the medication by gradually lowering the dosage until the antidepressant is no longer needed,” says Alpert. “For someone who has a more chronic depression, meaning one that has lasted for more than two years and has caused them to make attempts on their life, stopped them from working, or caused them to be hospitalized, we typically need to treat them longer before tapering the medication. At least three to five years after their depression is gone is recommended.”
The decision to stop taking antidepressants is one that should be made in consultation with a physician or psychiatrist as there can be serious side effects if done too quickly.
“Some people can have what we call discontinuation symptoms if they stop cold turkey. This is not because antidepressants are addictive but you have to be careful,” says Lam. “If stopped abruptly, people can feel jittery, they can have tremors, insomnia, mood worsening, and with certain medications some people report feeling electrical pulses throughout their body. It can be a terrible experience, that’s why we recommend a gradual lowering of the dosage.”
For some people though, stopping medication is not an option. “I always suggest taking a drug holiday to find out if you are fine without the medication,” says Serani. A drug holiday is a structured treatment interruption during which a patient stops taking a medication(s) for a period of time. “Unfortunately not everyone can function without medication. I have come off of medication twice to see if my depression would be there and sadly each time it creeps back in. I guess I’m just one of those people with a stubborn neurobiology. I just cannot be without the antidepressant.”
Optimizing recovery
Even though about 50 percent of people who take only medications to treat their depression do very well, there are other things that can be done to optimize one’s response and recovery rate.
“We always recommend exercise and making sure you have a proper diet,” says Lam. “For those with more severe depression, we usually recommend medications and psychotherapy. That can really help as well.”
Slater believes in the effectiveness of her antidepressants, but she also makes sure to stay healthy by exercising, eating right, and making sure she has a strong support network around her.
“I’m not a believer in just taking medications and just sitting on the couch waiting for it to work. I think you have to do a lot in addition to taking the medication. I do aerobics two to three times a week. I walk my dog an hour a day and I believe in having an active social life.”
Slater leads a happy, healthy and balanced life and she says the combination of medications, a healthy and active lifestyle, and a dedicated support network have made this all possible.
Melissa Churly is a freelance print journalist and graduate of Ryerson University. She is based in Mississauga, Ontario.
By Melissa Churly
Anchor Magazine
Deborah Serani always pictured herself as Eeyore, the despondent and downhearted donkey from Winnie the Pooh. “I was always just a sad sack,” says the Smithtown, New York resident. “And I didn’t even realize there was something wrong with me.”
Serani says that even as a child she was sad. It wasn’t until she had a major episode of depression while in college that she realized she had been feeling this way all her life. “I guess it was the fact that I had left the protective environment of home and the stress of school just really made me plummet into feeling very, very depressed. I had isolated myself, I wasn’t going to class, I was having panic attacks. I was just a mess.”
She dropped out of school for the semester and began psychotherapy. The therapy taught her a lot about her depression and gave her the tools she needed to get out of crisis. “But I just returned to the state I was in before the breakdown, which is what I thought was normal, and I stayed steady that way until I had my child some 20 years later.”
After a serious postpartum depression, Serani sought help again. This time she was prescribed antidepressants. “My psychiatrist prescribed me Prozac and within two weeks I was feeling so much better. Within two months, I was feeling better than I had ever felt before. I felt full and content and that’s when I realized that for 34 years I had been depressed.”
Today, Serani is still on antidepressants, but that hasn’t stopped her from being a successful psychologist and psychoanalyst who has her own private practice helping people with all forms of depression and mental illness. She believes in the effectiveness of antidepressants as she has seen first hand how successfully they can work.
Unraveling the placebo effect
But not everyone is as convinced. A few recent studies, including one published in the Journal of Affective Disorders (February, 2009), attributed 68 percent of the benefit from antidepressants to the placebo effect. In 2008, a similar paper appeared in PLoS Medicine (Public Library of Science) suggesting that widely used selective serotonin reuptake inhibitors (SSRIs), including Prozac, Paxil, and the serotonin-norepinephrine reuptake inhibitor (SNRI)Effexor offer no clinically significant benefit over placebos for patients with moderate or severe depression (SSRIs and SNRIs are antidepressants that affect serotonin levels in the brain).
According to Pierre Blier, MD, director of the Mood Disorders Research Unit at the University of Ottawa Institute of Mental Health Research, Ottawa, Ontario, a lot of these findings come from short-term studies and clinical trials that followed patients for only a few weeks. It generally takes about four to six weeks for patients on antidepressants to start to feel noticeably better and an additional six to nine months for these medications to have a lasting effect and to reduce the likelihood of relapse.
“When people are depressed, they need to be treated for months and sometimes years, so if you just look at the effectiveness of antidepressants over a couple of weeks you are getting a very narrow window on the disorder,” he says. “If I asked you to assess the effectiveness of an obesity treatment you’re not going to look at six weeks, you’re going to look at a couple of months or even a year. Even if the treatment makes a patient lose 10 pounds a week for six weeks that’s great, but if they put the 60 pounds back on in the next six months, the treatment is pretty useless. The same holds true for treating depression.”
Blier also attributes the placebo effect seen in many of the studies to the environment in which the study participants are placed. He points out that depressed patients who have been ill for weeks, months, even years―who haven’t been adequately cared for―are suddenly seen by a psychiatrist on a weekly basis, they have access to a research nurse, and they have a number they can call 24 hours a day to reach a psychiatrist if something goes wrong. If both the treatment group and the placebo group have access to these services, it “…has a big therapeutic effect. In such a setting, the placebo group is getting some kind of indirect treatment because of the support that the research team is providing,” says Blier. In other words, although it appears some patients on placebo improve as much as those in the treatment group, that result may be because of the supportive and nurturing environment that both groups are placed in. But this effect doesn’t last long, says Blier. “At the end of the study, those who continue on active medication for six months or more do really well; the effects of the antidepressant are very robust. In all of the recent papers reporting a controversial action of antidepressants there is not a single word about the long term effect of these drugs.”
Peter Kramer, MD, author and clinical professor of psychiatry and human behavior at Brown University, Providence, Rhode Island, agrees. “These medicines do have a pretty good track record. If the placebo effect were so strong we would see a lot more people responding to antidepressants. These placebo effects wash out over time and patients often become depressed again.”
Finding the right mix
Although antidepressants are effective in treating depression, some patients with certain types of depression may not respond as well to these medications, according to Jonathan Alpert, MD, an associate professor of psychiatry at Harvard Medical School in Boston.
An example of this can be seen in depressed patients who also suffer from anxiety. “Antidepressants appear to work quite effectively for all forms of unipolar depression such as major depressive disorder and dysthymia. But for certain forms of depression, like those that include severe anxiety, patients tend to not respond as well to the antidepressants compared to those without anxiety,” he says.
Bipolar depression is another form of depression where antidepressants aren’t as effective. In fact it can be dangerous to treat this form of depression with antidepressants alone as there is a significant risk of causing mania. “In just a matter of days, a patient can go from being deeply depressed to being extremely agitated and activated. We typically use a different class of medications called mood stabilizers or antipsychotics along with antidepressants to treat this disorder,” says Alpert.
For people with mild to moderate depression, antidepressant medications may not be the only solution according to Raymond Lam, MD, professor of psychiatry at the University of British Columbia, Vancouver, British Columbia. “Psychotherapy is as effective for treating mild depression as medications. In this case it’s kind of a preference whether people want to do therapy or take medication. They both seem to help.”
Antidepressants have come a long way since they were first discovered in the early 1950s. In terms of effectiveness, the medications have stayed the same, but Alpert argues the newer generation antidepressants are safer today.
“The older classes of antidepressants, although they are still occasionally used today, have very significant side effects and have a lot of interactions with other medications that are potentially dangerous, including effects on heart rhythms and blood pressure,” he says.
Weighing the pros and cons
Today’s antidepressants still have side effects, but they are generally more tolerable to patients. Common side effects include insomnia, weight gain or loss, nausea, diarrhea, constipation, decreased sex drive, and dry mouth.
“You just have to weigh the pros and cons of the medication and see if the side effects are something you can live with. With the medication I take I have increased sweating and weight gain. I say to myself "okay so {I gain weight}, yeah it’s not great but if I wasn’t on the medication I’d be thinner and not happy. I’d sooner choose happy and shapely than that,’” says Serani.
Over the last decade, Alpert says great progress has also been made in determining strategies for combining medications in order to increase the effectiveness of antidepressants. “Nowadays if somebody doesn’t respond to several antidepressants we’ll often consider combining antidepressants with other medications or other antidepressants. For example, the antipsychotic Abilify on its own does not treat depression, but when it’s combined with an antidepressant it was found that it boosts the effectiveness of the antidepressant,” he says.
A mixture of antidepressants and antipsychotic medications is what keeps Lynn Slater’s depression under control. “When I was just taking the antidepressant I still had some symptoms, so when they put me on the anti-psychotic it really took everything away,” says the 49-year-old Vancouver resident. Slater first became depressed as a child but it wasn’t until she was in college that she actually received any help. “For over 20 years I felt a lot of hopelessness, I remember a lot of deep despair, anxiety, and sleeplessness and as I got older things got worse.”
Blier and his Mood Disorders Research unit have also been investigating this form of treatment. “We’re treating depression now the way all physicians treat asthma. At the first episode people get at least two or three medications for asthma, well we’re doing the same thing for depression. We’re trying to change the standard of care so that patients don’t have to wait months or even years to feel better.”
Personalizing the process
Another area that is actively being researched to improve the effectiveness of antidepressants is finding ways to better predict how people respond to each medication. Even though there is a significant data set to show their overall effectiveness, doctors often don’t know which medications will be most tolerable and effective for specific patients. Each patient is different and responds to medications in a different way, so it’s typically a trial and error system.
“It’s called pharmacogenomics,” says Serani. “It’s where researchers study patients’ genes to predict how they might respond to drugs. It’s going to make it easier to select the right drug and the right quantity. It’s like long ago when they used to make glasses to either exaggerate or minimize [vision], then over time they got really good at it and now you can get an individual prescription that is tailored to your needs.” Scientists are still in the early stages of examining this type of ‘personalized medicine’ but it is a very active area of study right now. Although it will be many years before this technology is available it will contribute greatly to improving the quality of care for depressed patients and will be well worth the wait, says Serani.
Monitoring how a person is doing on a specific antidepressant is also a key component in improving the effectiveness of these medications says Kramer. “The key to pharmacology is a good working relationship between a doctor and a patient.” When starting a new medication regimen, it may be necessary for the doctor to see the patient every week or every couple of weeks so that the dose can be adjusted or the antidepressant changed to maximize the benefit and minimize the side effects. It’s also important for the patient to inform his psychiatrist of any discomfort, or if he feels the medication isn’t working. A relationship of trust between the patient and doctor is important to making this happen.
Having the support of her healthcare team is another aspect that contributed to Slater’s recovery. “I have been seeing my psychiatrist and my psychiatric nurse since 1986. Having those relationships for all these years has been really helpful. Although I don’t have to go and see them as often since I’m doing very well, just knowing that I can call them if I need any help is very important,” she says.
In order for antidepressants to really be effective, Blier says they have to be taken properly by patients.
“If antidepressants stay on the shelf, they can’t possibly work. Sometimes there are side effects that can cause the patient to stop taking them or maybe the dose needs to be adjusted to make it work better. Patients become discouraged by this, but I really recommend going back to your physician so it can be adjusted to make it more tolerable rather than just stopping the medication.”
The low compliance rate among patients may also be a reason antidepressants get a bad reputation says Lam. “Unfortunately, people stop the medications much too early because they are feeling better and they don’t feel like they need the medication anymore. Taking an antidepressant is kind of like taking an antibiotic. If you stop taking the antibiotic too early, even if you are feeling better, the infection can come back. It’s the same with depression.”
It’s also important to note that not everyone has to keep taking antidepressants forever.
“For people who have a single episode of depression that has lasted less than two years, typically we continue to treat them for another six to nine months after all of the depressive symptoms are gone. At that point we will attempt to taper the medication by gradually lowering the dosage until the antidepressant is no longer needed,” says Alpert. “For someone who has a more chronic depression, meaning one that has lasted for more than two years and has caused them to make attempts on their life, stopped them from working, or caused them to be hospitalized, we typically need to treat them longer before tapering the medication. At least three to five years after their depression is gone is recommended.”
The decision to stop taking antidepressants is one that should be made in consultation with a physician or psychiatrist as there can be serious side effects if done too quickly.
“Some people can have what we call discontinuation symptoms if they stop cold turkey. This is not because antidepressants are addictive but you have to be careful,” says Lam. “If stopped abruptly, people can feel jittery, they can have tremors, insomnia, mood worsening, and with certain medications some people report feeling electrical pulses throughout their body. It can be a terrible experience, that’s why we recommend a gradual lowering of the dosage.”
For some people though, stopping medication is not an option. “I always suggest taking a drug holiday to find out if you are fine without the medication,” says Serani. A drug holiday is a structured treatment interruption during which a patient stops taking a medication(s) for a period of time. “Unfortunately not everyone can function without medication. I have come off of medication twice to see if my depression would be there and sadly each time it creeps back in. I guess I’m just one of those people with a stubborn neurobiology. I just cannot be without the antidepressant.”
Optimizing recovery
Even though about 50 percent of people who take only medications to treat their depression do very well, there are other things that can be done to optimize one’s response and recovery rate.
“We always recommend exercise and making sure you have a proper diet,” says Lam. “For those with more severe depression, we usually recommend medications and psychotherapy. That can really help as well.”
Slater believes in the effectiveness of her antidepressants, but she also makes sure to stay healthy by exercising, eating right, and making sure she has a strong support network around her.
“I’m not a believer in just taking medications and just sitting on the couch waiting for it to work. I think you have to do a lot in addition to taking the medication. I do aerobics two to three times a week. I walk my dog an hour a day and I believe in having an active social life.”
Slater leads a happy, healthy and balanced life and she says the combination of medications, a healthy and active lifestyle, and a dedicated support network have made this all possible.
Melissa Churly is a freelance print journalist and graduate of Ryerson University. She is based in Mississauga, Ontario.
Last edited:
