Antidepressants can improve the symptoms of depression. But they can also cause serious side effects, so you don't want to take one if you don't have to. The information in this report can help you decide-with your doctor or mental health professional-whether an antidepressant might be right for you, and if so, which one.
Retail prices for commonly prescribed antidepressants range from about $21 a month, and sometimes even less, to more than $1,000 a month. This report shows how you can save more than $100 a month or $1,200 a year, if you have to take an antidepressant regularly.
Here's a thumbnail guide to help you decide if you should consider medication:
- It is normal to feel "down" or "blue" in the wake of a stressful life event, such as the death of someone close, a divorce, or a job loss. If you are still able to function and have no history of depression, your symptoms will usually ease on their own within a few months, aided, if necessary, by family support and professional counseling, without the use of an antidepressant.
- If you are not functioning well and your symptoms (see Table 1) have lasted for a few weeks, you are more likely to be a candidate for an antidepressant. That is especially true if there is no apparent reason for you to be depressed or if you have had repeated episodes of depression.
Your doctor may not be aware of price differences between medicines, so be cautious if he or she offers you a free sample of an antidepressant that they happen to have in their office. While getting a medication for free may be tempting, the drug may not be the right one for you. Individual needs vary and people respond to antidepressants quite differently. Some have to try two or three antidepressants before finding one that works.
Taking effectiveness, safety, side effects, and cost into account, we have chosen five Consumer Reports Best Buy Drugs as initial options to consider for depression:
- Generic bupropion
- Generic citalopram
- Generic escitalopram
- Generic fluoxetine
- Generic sertraline
These medicines are substantially less expensive than brand-name antidepressants and are equally as effective. Both bupropion and escitalopram are more expensive than the others, so if cost is a concern, that may be something to consider when choosing an antidepressant for the first time. If you have drug coverage, talk with your doctor about finding the antidepressant that has the lowest out-of-pocket cost under your insurance plan.
Other important considerations:
- Start with the lowest therapeutic dose. If it doesn't help within six to eight weeks or causes side effects, talk with your doctor about changing the dose or switching to another antidepressant.
- If you took an antidepressant before and it worked, you may want to stick with that one.
- Tell your doctor whether the differences in side effects among the antidepressants are important to you. (See Table 3.)
- If you already take an antidepressant and it is working for you, we don't recommend that you switch to another one.
This report was published in September 2013.
- Section 1: Welcome
- Section 2: What Are Antidepressants and Who Needs Them?
- Section 3: Choosing an Antidepressant - Our Best Buy Picks
- Section 4: The Evidence
- Section 5: Tips to Talking With Your Doctor
- Section 6: How We Picked the Best Buy Antidepressants
- Section 7: Sharing This Report
- Section 8: About Us
- Section 9: References
This report on prescription drugs to treat depression is part of a Consumer Reports project to help you find safe, effective medicines that give you the most value for your health-care dollar. To learn more about the project and other drugs we've evaluated, go to www. CRBestBuyDrugs.org.
We focus on the most commonly prescribed antidepressants to treat depression and other mood and emotional disorders. In 2012, antidepressants were one of the most commonly prescribed classes of drugs in the U.S., and one antidepressant-Cymbalta-was the fifth top selling of all drugs with $4.7 billion in sales, according to IMS Health, a healthcare technology and information company. The first of these so-called "second-generation antidepressants"-bupropion (Wellbutrin)-became available in 1985. Prozac, approved in 1987, is also in this class. Those medicines were a significant advance over drugs used to treat depression up to 1985, for one chief reason: They caused fewer serious side effects. However, our analysis finds that they are no more effective than the older medicines, many of which are still available and used with success in some circumstances. An example of the older medications are the tricyclic antidepressants, such as amitriptyline, nortriptyline, imipramine, and desipramine.
Twelve drugs were included in our analysis. They are:
|Generic Name||Brand Name(s)||Available as a generic?|
|1. Bupropion||Wellbutrin, Wellbutrin SR, Budeprion SR, Wellbutrin XL||Yes|
|6. Fluoxetine||Prozac, Prozac Weekly, Sarafem||Yes|
|7. Fluvoxamine||Luvox, Luvox CR||Yes|
|9. Nefazodone||Brand name no longer on the market||Yes|
|10. Paroxetine||Paxil, Paxil CR, Pexeva||Yes|
|12. Venlafaxine||Effexor, Effexor XR||Yes|
*The generic version of this drug must be specifically requested by your doctor.
Eleven of the 12 medicines-bupropion, citalopram, desvenlafaxine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, and venlafaxine-are now available as less-costly generic drugs in some dosage forms. Several are also available in liquid formulations. Good to know: In late 2012, the FDA ordered the withdrawal of the 300 mg dose of generic bupropion, sold under the name Budeprion XL and made by Impax Laboratories and Teva Pharmaceuticals, because testing had found that it was not released into the bloodstream at the same rate and in the same amount as its brand-name counterpart, Wellbutrin XL. The move did not apply to Wellbutrin XL, or other generic versions of bupropion.
A generic version of Pristiq was recently approved by the FDA. However, because it contains a different salt than the brand-name drug, the generic will not be automatically substituted for by your pharmacist. If your doctor prescribes you Pristiq but you would like to take the generic, be sure to have him or her write the prescription specifically for desvenlafaxine.
Meanwhile, a new antidepressant, vilazodone (Viibryd), was approved by the FDA in January 2011, but it is not included in our analysis. Although other analyses suggest it has similar side effects as other SSRI antidepressants, it doesn't have their long track record. And since there is no generic version available yet, it is expensive, so our Best Buy picks are better options to consider first.
Note: Nefazodone (Serzone) has been associated with reports of severe liver damage. In 2004, the manufacturers of the branded version stopped producing it. The generic version of this drug is still available. We recommend avoiding nefazodone if at all possible until this important safety issue is resolved. (We discuss this drug in more detail on section 3).
Many of the second-generation antidepressants have been approved for the treatment of other psychiatric conditions besides depression, such as anxiety, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, and social phobia. In this report, we focus only on their use in the treatment of depression in adults.
Other treatments for depression are available, most notably psychotherapy or other professional counseling, and transcranial magnetic stimulation. In addition, some people with severe depression may benefit from electroconvulsive therapy or hospitalization to undergo intensive treatment. This report does not evaluate those treatments or compare them with the use of antidepressants for outpatients. Table 2 presents treatment options for depression.
In any given year, nearly 7 percent of the U.S. adult population 18 and over-some 14.8 million people- will have a depressive illness that warrants treatment, according to the National Institute of Mental Health. For reasons that remain unclear, women appear to develop depression at about twice the rate as men. About 2 percent of children between the ages of 3 and 17 develop depression, according to the Centers for Disease Control and Prevention. Evidence indicates that today only about 51 percent of the people with major depression get any treatment at all, and only 21 percent receive appropriate treatment, meaning that the majority are not getting the therapies that could bring them relief.
This report is based on a comprehensive expert analysis of the medical evidence on antidepressants. There's more information on section 6 and at www.CRBestBuyDrugs.org on how we conducted our evaluation.
This report was updated in September 2013.
What Are Antidepressants and Who Needs Them?
Antidepressants are thought to work primarily by altering levels of chemicals in the brain called neurotransmitters. The most important of these are serotonin, norepinephrine, and dopamine.
There are several different types of antidepressants among the 12 drugs listed on section 1. The main group of second-generation antidepressants is called the "selective serotonin reuptake inhibitors," or SSRIs for short. As the name implies, they appear to affect mainly serotonin (a neurotransmitter) levels in the brain. This group includes citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine* (Luvox, Luvox CR), paroxetine (Paxil), and sertraline (Zoloft). *Note that while fluvoxamine is an SSRI, it is not FDA-approved for treating depression. It is only approved for treating social anxiety disorder and obsessive-compulsive disorder, but doctors do prescribe it "off label" to treat depression.
The other antidepressants-bupropion (Wellbutrin), desvenlafaxine (Pristiq), duloxetine (Cymbalta), mirtazapine (Remeron), and venlafaxine (Effexor)- appear to work by affecting brain levels of one, two, or possibly three neurotransmitters. Knowing this can help you understand why your doctor may prescribe another antidepressant for you if the first one doesn't work. Our brain chemistries may be just as unique as our appearances and personalities.
Certain generic antidepressants may cost as little as $4 for a month's supply through generic drug programs offered by major chain stores, such as Kroger, Sam's Club, Target, and Walmart. For an even better bargain, you may be able to obtain a three-month supply for $10 through these programs. We note in the price chart starting on Antidepressant Cost Comparison table under the Drug Comparison tab which generic antidepressants are likely available through these programs. Some stores, such as CVS and Walgreens, may require a membership fee to participate and might charge different prices. There might be other restrictions too, so check the details carefully to make sure your drug and dose are covered.
What is Depression?
Being sad, blue, or unhappy at times is a normal part of life. But being seriously "down" or depressed for a prolonged period-more than two weeks or so-may not be normal and can usually be helped with appropriate treatment. Depression is not simply unhappiness. Indeed, prolonged depression should be viewed as an illness like any other, no different than an infection, cancer, diabetes, or heart disease. The symptoms are distinct (see Table 1) and can be triggered by adverse life events, illness, or arise for no apparent reason. Whatever the cause, the symptoms feel equally painful and the biological changes in the body and brain are the same.
Depression can be recurrent and chronic, and it can sometimes run in families as a result of genetic inheritance. And no matter what the cause, if left untreated, it can be deadly. People with untreated depression are at much greater risk of premature death, not only from suicide, but also from a host of other illnesses.
The difficulty comes in determining the difference between a normal slump, even one that may last a while, and serious depression. Table 2 can help you determine the type of depression you may have. It is a brief guide to the different kinds and levels of depression and treatment options.
|Table 1. The Symptoms of Depression|
People experience depression symptoms differently. But generally, if you have five or more of the following symptoms persistently for several weeks or longer, you may have serious or so-called "major" depression that could warrant treatment with medication. That is especially likely if you have a history of depression and there has been no "triggering" event or trauma in your life, such as a death in the family, a job loss, a divorce, or marital problems.
The bottom line is this:
- If you have some of the symptoms in Table 1 but they are not particularly severe and you are functioning OK in life, you may have mild depression. If your "blues" seem to be triggered by a specific event, trauma, or transition in your life but you have no history of depression, you may also have mild "situational" depression. In both cases, you should think twice before taking an antidepressant. Experts believe that too many people whose temporary depression can resolve on its own in a few weeks are prescribed an antidepressant.
- If you have five or more of the symptoms in Table 1, for most of the time almost everyday for two weeks or longer-and you are not functioning well in life-you are likely a candidate for an antidepressant. This is true even if your depression was triggered by a life event or trauma, and is especially true if you have had previous episodes of depression. Millions of people who have such symptoms are not getting the treatment they need.
- If you have experienced several of the symptoms in Table 1 at a low-grade level for months, you should see a doctor or therapist. You may want to try psychotherapy or other counseling first, especially if your symptoms can be linked to a definable stressor (such as problems with your marriage, an unhappy work situation, or the illness of someone you care about). If that doesn't help, consider an antidepressant.
Some studies have found-and many experts believe- that antidepressants often work best in combination with psychotherapy lasting at least several months. But antidepressants on their own play an important role in our culture. That's because not everyone has access to, can afford, or accepts that psychotherapy can help.
On the other hand, many people prefer to try psychotherapy alone, or they are afraid of the side effects and skeptical of the benefits of antidepressant drugs. We would encourage you to seek out whichever type of treatment or combination of treatments you are most comfortable with.
|Table 2. Types and Levels of Depression|
|"Situational" or "reactive" sadness, grief, or depression||
|Low-grade depression, also called dysthymia||
Choosing an Antidepressant - Our Best Buy Picks
Second-generation antidepressants have been proven to help relieve the symptoms of depression in 55 to 70 percent of the people who take them. None have clearly been shown to be any more effective in relieving symptoms or bringing about a full recovery than any other when taken in comparable doses.
However, one meta-analysis-the combined results of many different studies-found that escitalopram and sertraline were superior to other second-generation antidepressants when considering both effectiveness and safety. But you should know that some experts have disagreed with this conclusion, pointing out that the study had several limitations that make the results unreliable. For example, it combined the findings of several studies that measured patient responses to the medicines using different methods, so they say it is problematic to lump the results together. And while a few of the studies included in the analysis were done well, others were of lower quality. Another weakness is that some patients involved in the studies may have had more severe depression than others; for example, some were treated in a hospital, while others were treated on an outpatient basis, and some also suffered from anxiety.
Other analyses - including ones conducted by the Drug Effectiveness Review Project at Oregon's Health & Science University and the Agency for Healthcare Research and Quality, which this Best Buy Drugs report is based upon-have concluded that no one second-generation antidepressant is clearly superior to another. That conclusion is also echoed by the American College of Physicians' current depression treatment guidelines, which recommends that antidepressants be chosen based on cost and the known differences in side effects.
Antidepressants differ greatly in both cost and the side effects they cause. Retail prices vary from about $21 a month, and sometimes even less, to more than $1,000 a month (see Antidepressant Cost Comparison table).
The majority of people who take antidepressants (63 percent) experience at least one side effect, according to a 2011 analysis conducted by the Agency for Healthcare Research and Quality, upon which this report is based.
Most tolerate mild side effects without much difficulty. But a sizable minority-up to 12 percent-find the side effects so intolerable that they stop taking the medicine.
Table 3 lists some of the side effects of antidepressants. Those related to one's sex life are many people's chief concern, but are not dangerous. Pharmaceutical company information and some studies indicate that between 5 to 15 percent of the people who take antidepressants can expect to experience a decline in interest in sex or difficulty reaching erection or orgasm. Some studies suggest the rate can be as high as 60 percent. One of the largest surveys to date, conducted by Consumer Reports and published in the July 2010 issue of Consumer Reports magazine found that 23 to 36 percent of respondents had sexual problems associated with the use of some antidepressants. Since depression itself can make people lose interest in sex, it is important to determine whether it is the antidepressant or the depressive illness that is causing the problem.
Increases in agitation, anxiety, and suicide are more worrisome side effects, although they are relatively rare. If you have such symptoms, you should contact your doctor immediately. Suicide is rare, occurring in approximately 1 in 8,000 people who take antidepressants. Suicidal thoughts, however, are more common, occurring in 1 in 166. Adolescents and young adults have the most risk of these serious side effects, while recent studies indicate that older adults who take antidepressants do not face an increased risk. Suicidal thoughts can be a symptom of depression itself, so if you experience those, contact your healthcare professional immediately to determine whether it's due to the medication and if you should switch to a different drug or treatment strategy.
|Table 3. Side Effects|
side effects that
usually go away
in time or are
More serious side effects
that can be annoying
or dangerous. If they
persist, you may need
to switch drugs:
There is some evidence that antidepressants may increase the risk of type 2 diabetes, fractures of the hip or other bones, and gastrointestinal bleeding, especially when used with nonsteroidal antiinflammatory drugs, such as ibuprofen (Advil and generics) and naproxen (Aleve and generics).
Talk with your doctor about the difference between antidepressants in terms of side effects. This may well affect your choice. Table 4 summarizes the evidence on the effectiveness of antidepressants and the rate at which people stopped taking each antidepressant because of side effects. The table also has comments on some of the strengths and identified problems with each drug.
When you talk with a doctor about the antidepressant and dosage that is right for you, you should discuss:
- The scope and severity of your symptoms, especially any thoughts of suicide. Be specific; consider writing down symptoms before your discussion.
- Any prior use of and response to an antidepressant or drug to treat anxiety or other psychiatric illness.
- Other treatments you are considering, such as psychotherapy or counseling, or dietary supplements such as St. John's wort.
- Side effects and choosing a low dose, which might reduce the risk of them.
- Side effects you fear or would prefer to avoid.
- The rate at which people stop taking various antidepressants, as listed in Table 4.
- Cost (See Antidepressant Cost Comparison table).
- Your insurance coverage (if you have it) and which drugs may be "preferred" under that plan, for which you may pay less out-of-pocket.
Taking the evidence on effectiveness, safety, side effects, and cost into account, we have chosen five Consumer Reports Best Buy Drugs as initial options to consider:
- Generic bupropion
- Generic citalopram
- Generic escitalopram
- Generic fluoxetine
- Generic sertraline
Those medicines are substantially less expensive than the brand-name antidepressants we evaluate in this report, and are as effective and safe as any of them for initial treatment. They are also affordable options if you need to try another antidepressant because the first one your doctor prescribed did not help or caused unacceptable side effects. Both bupropion and escitalopram are more expensive than the others, so if cost is a concern, that may be something to consider when choosing an antidepressant for the first time. If you have drug coverage, talk with your doctor about finding the antidepressant that has the lowest out-of pocket cost under your insurance plan.
Citalopram, escitalopram, fluoxetine, and sertraline are also available in liquid formulations.
All five Best Buy recommendations are generic drugs. There is no reason to take the brand-name version of any of those medicines. There are other generics available at comparable cost to our Best Buy Drugs. (See Antidepressant Cost Comparison table.) Our choice of the five was based on the strength of the evidence for effectiveness, the risk of side effects, the risk of having to discontinue the drug, and other unique factors as identified in Table 4.
Several antidepressants discussed in this report are approved to treat people diagnosed with a combination of anxiety and depression. Our Best Buy picks are for those whose diagnosis is depression only (though some mild anxiety symptoms may be present). Talk with your doctor about the best medicine for you if he or she identifies you as having a combined depression/ anxiety illness.
|Table 4. Effectiveness and Tolerability of Antidepressants|
|Generic Name||Brand Name||Response to Treatment (percent)1||People who Stopped Taking Drug Because of Side Effects (percent)2||Comments/Special Notes3|
|Nefazodone||Generic only||47-59||Insufficient data||
- Response defined as at least 50 percent reduction in depression symptoms on behavioral and emotion rating scales.
- Numbers are the lower and upper quarter percentile of discontinuation rates from studies.
- Based on multiple studies and combined analysis of studies, or from the drug's product label information. Statements made in reference to all other drugs listed except where noted. List is not intended to be comprehensive.
- The other SSRIs were fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft).
- Higher than fluoxetine (Prozac), sertraline (Zoloft), and fluvoxamine (Luvox CR) in controlled trials. Highest rate of sexual side effects (53 percent) in a 2004 Consumer Reports survey of 1,664 people when compared with bupropion (Wellbutrin) (21 percent); fluoxetine (Prozac) (41 percent); citalopram (Celexa) (45 percent); sertraline (Zoloft) (46 percent); and venlafaxine (Effexor) (51 percent).
Be aware that there is a widely accepted practice in prescribing antidepressants. Doctors will-and should-try the lowest therapeutic dose initially. They will then monitor your response-mainly how you feel, how you are functioning, your symptoms, and any side effects. It's rare for antidepressants to have any immediate effect. Most people do not feel any different for several weeks, and a response can take as long as six weeks. Your response may build over time, too.
Response is also quite subjective; that is, some people are pleased with any improvement, while others are not satisfied until they feel a substantial reduction in their symptoms.
If you do not respond to the first drug tried-and studies suggest that about 30 to 40 percent of people don't-your doctor can (a) increase the dose of that drug or (b) switch you to another one. Typically, he or she will increase the dose first, unless you have had side effects that are severe or unacceptable. They can then switch you to a comparable or perhaps slightly higher dose of another antidepressant. It's not uncommon to try as many as three or even four antidepressants before you find one that works. Once you and your doctor find an antidepressant that works for you, your doctor may increase the dose to see if you can tolerate it and experience more improvement without side effects.
Once you and your doctor find an antidepressant that works for you, your doctor may increase the dose to see if you can tolerate it and experience more improvement without side effects.
Venlafaxine (Effexor) is more often used as a "second line" drug in people who have not responded to other antidepressants, particularly those drugs in the subclass known as selective serotonin reuptake inhibitors, or SSRIs. If your doctor recommends this drug, you should know that it may increase blood pressure and heart rate. So if you start taking venlafaxine, your blood pressure should be monitored. If you do experience a rise in blood pressure that persists, you may have to either lower the dose or stop taking the drug. And if you have other conditions, including an overactive thyroid, heart failure, or have recently had a heart attack-any of which can make you particularly vulnerable to problems from an increased heart rate- you should avoid the drug.
Given those risks, we advise against venlafaxine as initial therapy. In addition, we recommend that people with high blood pressure and heart disease avoid the medicine. If you are currently taking venlafaxine, you should talk with your doctor.
Desvenlafaxine (Pristiq) and duloxetine (Cymbalta), two of the newest antidepressants, are chemically similar to venlafaxine. Both can increase blood pressure, but they have not been linked to an elevated heart rate. Desvenlafaxine was approved in 2008, so it does not have the long track record of some of the other antidepressants, and its safety profile is not fully established. We recommend caution.
Also, you should know that there have been reports of people taking nefazodone who suffered liver failure that resulted in death or the need for a liver transplant. The available studies involving nefazodone are insufficient to determine if it does or does not cause liver damage. The maker of the brand-name version, Serzone, discontinued the drug in 2004 after it was associated with reports of liver toxicity, but generic versions of the drug are still available. An advantage of nefazodone is that it carries a lower risk of sleep problems and sexual dysfunction side effects than the other antidepressants. But given the potential seriousness of the liver problems, we recommend avoiding nefazodone if at all possible until this important safety issue is resolved. If the antidepressant you're taking is causing you sleep disturbances or sexual side effects, we advise you to work with your doctor to find another antidepressant (other than nefazodone) that you tolerate better, or other solutions to alleviate these problems.
When taking an antidepressant, you should:
- Take the medication as scheduled according to the instructions on the label or package insert. They have to be taken daily to be effective, not just when you feel bad or low.
- Never take more than specified without telling your doctor. This raises your risk of side effects, and most notably could trigger agitation or distressing feelings of anxiety.
- Never stop taking it on your own without consulting your doctor. Sudden withdrawal can cause uncomfortable, distressing, and even dangerous symptoms if you have been taking the drug for a while. These include agitation, nervousness, anxiety, tremors, irritability and insomnia, dizziness, and nausea.
- When starting an antidepressant (or any new drug, for that matter), always ask about possible drug interactions with medications and dietary supplements you are already taking.
Antidepressant Use in Children and Teenagers
The FDA now requires drug makers to put warnings (detailed descriptions of the medicine's intended use, safety, and efficacy) on labels for all antidepressants, stating that an increased risk of suicidal thinking may occur in children, teenagers, and young adults taking an antidepressant. This action took place after studies found that there was double the risk of suicidal thoughts in children and teenagers who took the drugs compared with those who took dummy pills. Such thoughts occurred in about four out of every 100 children and teenagers who took an antidepressant compared with two out of 100 who took a placebo, and there were no actual suicides in the studies the agency reviewed.
The studies were too small to compare the risk between drugs, so the agency decided to require that all antidepressants carry the warning labels and that ads and promotions for the drugs cite this risk.
The FDA also urged that children and teenagers prescribed antidepressants be monitored by a doctor or mental-health professional much more closely-weekly during the first four weeks of treatment-than was the norm before the findings established this alarming link. The FDA has also issued a medication guide on antidepressant medicines that should be given to patients by their physicians.
It is also important that families and caregivers observe patients closely and communicate with their doctors. Parents and caregivers should monitor their children for signs their depression is getting worse as well as agitation, irritability, and unusual changes in behavior, especially during the initial few months of antidepressant therapy, or when the dosage changes.
Parents who suspect that their child or teenager may be depressed should seek the help of a doctor or mental-health professional. We advise the following:
- Confirm the diagnosis. Depression can be more difficult to detect in children and teenagers.
- Be especially alert to any signs of suicidal thinking or actions.
- Consider psychotherapy or counseling.
- Consider an antidepressant (fluoxetine to start) if a doctor advises it, especially if other treatments have not helped.
- Use antidepressants with caution, and learn about the risks and side effects in children and teenagers.
To date, only fluoxetine (Prozac and generic) is FDA-approved for use in both children and teens. Escitalopram (Lexapro and generic) is FDA-approved for use in teens.
You may be able to save money by splitting your antidepressant pills or tablets. As you can see from Antidepressant Cost Comparison table, some antidepressants are more expensive at higher doses, but usually not twice as much. And higher doses of some antidepressants cost about the same as a lower dose.
Some antidepressant pills can be safely split. But you should talk with your doctor before you do this. Some people find splitting pills to be confusing or cumbersome to do. Other types of pills, including long-acting, sustained-release, or continuous-delivery pills, should never be split.
If you and your doctor agree that you can safely split your pills, you should use a pill splitter to make certain that the two halves are the same size and will therefore provide you with the correct dose. The devices cost $5 to $10 and are widely available.
This section presents more detailed information on the effectiveness and safety of antidepressants.
This report is based on analyses of the scientific evidence for second-generation antidepressants. Overall, 8,558 studies and research articles dealing with antidepressant use were identified and screened. All were published between 1980 and October 2012. From these, the analysis focused on 274 studies that included 204 controlled clinical trials, and 56 observational, cross-cutting, or studies of other design. An additional 205 articles were reviewed for background information pertinent to antidepressant chemistry, biology, and clinical use.
How Effective Are Antidepressants?
Antidepressants are moderately effective medicines, with a wide variety of responses. Their effectiveness and benefits are assessed based on four criteria:
- Response to treatment, with at least a 50 percent improvement in depressive symptoms on a rating scale indicating a "positive" response
- Remission of symptoms
- Speed of response
- Quality of life
On average, 55 to 70 percent of the people who take antidepressants can expect at least a 50 percent improvement or decrease in their symptoms. This is measured using a rigorous rating scale but is still highly subjective. Response is quite different among individuals, as is the length of treatment required. Some people respond within a few weeks and experience an almost complete elimination of their symptoms within a few months. Others may get only about a 50 percent improvement even after months of taking an antidepressant. Roughly 30 to 45 percent of people fail to respond to treatment with an antidepressant.
Also, of those who do respond, some can gradually stop taking their medicine six months or so after they improve, while others must take an antidepressant for long periods to keep symptoms at bay or prevent a relapse.
The antidepressants discussed in this report do not differ overall in the response they yield, though, as discussed, people respond to drugs differently. And no evidence indicates that any antidepressant is more effective than another in comparable doses. Larger doses of each of them can sometimes, but not always, improve the chances of response, but at the same time, larger doses increase (sometimes sharply) the risk of side effects.
More extensive studies have been conducted on some antidepressants than on others. Unfortunately, not all of the antidepressants have been directly compared with others in terms of either effectiveness or safety.
In addition, most studies of antidepressants are short-term, lasting only six to 12 weeks. Such a time frame does not allow for an assessment of long-term response. The few longer-term studies have found a highly variable success rate in achieving "full recovery" in particular. They indicate that between 30 and 60 percent of the people "fully recover" from depression after taking an antidepressant alone. Here as well, no particular antidepressant has an edge over any other.
As we have already noted, a recent meta-analysis concluded that escitalopram and sertraline were superior to other second-generation antidepressants. But some experts have pointed out that this study had several limitations that make the results unreliable. In addition, other analyses have concluded that no one second-generation antidepressant is better than any of the others. So we recommend that the choice of antidepressant should be based on cost and the known differences in side effects, which are discussed on the following page.
Studies have found that the so-called "second-generation" antidepressants that are the subject of this report are as effective as and much safer-in terms of the risks of serious consequences as a result of overdose-than older medicines for depression, the tricyclic antidepressants and monoamine oxidase inhibitors, or MAOIs. Second-generation antidepressants are also usually better tolerated.
Although marketing campaigns often tout the benefits of antidepressants for people who suffer from both depression and anxiety or other symptoms, there are few studies comparing drugs head-to-head in this regard and the available evidence does not indicate a clear advantage of one antidepressant over another in such people.
Some antidepressants do act faster than others. In particular, mirtazapine (Remeron) shows a faster action in multiple studies compared with some SSRIs - fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft). The makers of venlafaxine (Effexor) claim a similar fast onset but the evidence is less clear than for mirtazapine (Remeron). In the case of Remeron, a faster-acting response means a noticeable improvement of symptoms one to two weeks earlier than with the compared drugs. Unfortunately, this advantage is sometimes offset by an increased weight gain that many patients find disturbing.
How Safe Are Antidepressants?
By and large, the evidence indicates that people should take antidepressants with caution, fully aware of the risks, and pay close attention to side effects. That said, they have been used safely by millions of people for 20 years.
The vast majority of people who take an antidepressant (up to 63 percent) will experience at least one side effect. Most of them are minor. Diarrhea, dizziness, dry mouth, fatigue, headache, nausea, sexual side effects, sweating, tremors, and weight changes are the most common. Sometimes they are very severe, making it necessary to discontinue the medication and try another.
Antidepressants differ in the side effects they cause, and this can be a basis for choosing one over another, or weighing the risks against the benefits.
As presented in Table 4, bupropion (Wellbutrin) has a lower rate of sexual side effects and paroxetine (Paxil) has the highest; venlafaxine (Effexor) leads more often to nausea and vomiting, and elevations in blood pressure and heart rate; duloxetine (Cymbalta) has been associated with liver failure, including some cases that were fatal, so it should not be taken by people with liver disease or who consume substantial amounts of alcohol; sertraline (Zoloft) has higher rates of diarrhea; and mirtazapine (Remeron) leads more often to weight gain. High doses-and especially overdoses-of bupropion (Wellbutrin) have been linked to seizures, so most doctors don't prescribe it to people who have a history of seizures.
All antidepressants can cause serious side effects, too. The most serious of them are agitation, anxiety, confusion, panic, and suicidal thinking. (For most people, antidepressants reduce suicidal thinking. But for a small percentage of people, they may increase it.) These symptoms can also occur-in fact, are more likely to occur-if you stop taking an antidepressant suddenly, a condition called "discontinuation syndrome."
Antidepressants can also cause very rare but potentially life-threatening side effects. They include seizures and dangerously low blood-sodium levels. If you have ever experienced any of these conditions before or feel that you may have an increased risk, tell your doctor before he or she prescribes an antidepressant for you.
Antidepressants can interact with other medicines or dietary supplements (most notably St. John's wort) in ways that can be dangerous. Some drugs should never be used in combination with second-generation antidepressants. They include:
- Older antidepressant medications known as MAOIs, such as selegiline (Eldepryl), isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate)
- Certain psychiatric drugs, such as thioridazine and pimozide (Orap)
In some cases, your doctor may recommend that you take a specific second-generation antidepressant because of evidence that it is less likely to interact with another medicine you are taking. The main drugs to be concerned about are:
- Blood thinners, such as warfarin (Coumadin)
- Seizure medications, such as carbamazepine (Tegretol) or phenytoin (Dilantin)
- Psychiatric medications, such as lithium (Eskalith or Lithobid), haloperidol (Haldol), or risperidone (Risperdal)
- Antianxiety medications, such as alprazolam (Xanax), diazepam (Valium), or lorazepam (Ativan)
- Certain antibiotics such as ciprofloxacin (Cipro) and erythromycin, or antifungal medicines, such as ketoconazole (Nizoral)
- Migraine medications, such as sumatriptan (Imitrex), zolmitriptan (Zomig), or others in this class of drugs known as "triptans"
If you are taking other medicines with a second-generation antidepressant, you should tell your doctor.
You should also be aware that there's conflicting evidence from two recent studies about the potential for some antidepressants to negatively interact with the breast cancer drug tamoxifen. Many women may be taking both drugs because antidepressants are also sometimes used to treat hot flashes due to menopause. A U.S. study found that women taking tamoxifen and SSRI antidepressants had an increased rate of recurrence of their cancer over two years. But another study done in the Netherlands found no increased rate of cancer recurrence in women taking both tamoxifen and antidepressants for four years.
Until these conflicting results are resolved, we would recommend that if you are taking tamoxifen, you should avoid SSRI antidepressants for treating hot flashes and talk to your doctor about using other options. If you need an SSRI antidepressant for depression, two drugs-citalopram and escitalopram- may be the least likely to negatively interact with tamoxifen, but studies to support this have not yet been done. In some cases, it might be better to use a different type of antidepressant than an SSRI.
One concern with mixing antidepressants with other medications is a potentially life-threatening but rare condition called "serotonin syndrome" that occurs when serotonin levels in your body become too high.
This can occur with antidepressants alone, but increasing the dosage or adding a new drug or dietary supplement to your regimen can also cause it. The main drugs or dietary supplements of concern are antipsychotics, the antibiotic linezolid, MAOIs, migraine "triptan" medicines such as sumatriptan (Imitrex and generics) and rizatriptan (Maxalt and generics), tryptophan, and the herbal St. John's wort.
Symptoms of serotonin syndrome include diarrhea, dilated pupils, fever, rapid or irregular heartbeat, seizures, shivering, or unconsciousness. If you develop any of these within hours after increasing your dosage or taking a new drug or dietary supplement, contact your physician or go to an emergency room immediately.
It's also wise to limit or eliminate your use of alcohol while taking an antidepressant. To begin with, alcohol is a depressant (after the initial "high") and it can worsen depression. Second, heavy alcohol use can damage your liver so that an antidepressant becomes toxic.
Age, Race, and Gender Differences
People older than 65 and members of various ethnic groups have been underrepresented in most studies of antidepressants. The available evidence suggests that antidepressants do not work as well in older people (65 and older) or those who are medically ill, and the medications might take longer to work in the elderly. However, some studies indicate that older adults who take antidepressants have a reduced risk of suicide and suicidal thoughts.
Overall, the existing evidence does not indicate that any antidepressant is more or less effective in older patients, people of any particular race or gender, or in patients who have other diseases. Recent studies, however, have raised caution about the safety and effectiveness of antidepressants in children and adolescents, as discussed on section 3.
Tips to Talking With Your Doctor
It's important for you to know that the information we present here is not meant to substitute for a doctor's judgment. But we hope it will help you and your doctor arrive at a decision about which antidepressant and dose is best for you, if one is warranted at all, and which gives you the most value for your health-care dollar.
1. Mention cost to your doctor.
Bear in mind that many people are reluctant to discuss the cost of medicines with their doctor, and that studies have found that doctors do not routinely take price into account when prescribing medicines. Unless you bring it up, your doctor may assume that cost is not a factor for you.
2. Ask about older medications.
Many people (including physicians) think that newer drugs are better. While that's a natural assumption to make, it's not always true. Studies consistently find that many older medicines are as good as, and in some cases better than, newer medicines. Think of them as "tried and true," particularly when it comes to their safety record. Newer drugs have not yet met the test of time, and unexpected problems can and do crop up once they hit the market. Of course, some newer prescription drugs are indeed more effective and safer. Talk with your doctor about newer vs. older medicines, including generic drugs.
3. Consider generic drugs.
Prescription medicines go "generic" when a company's patents on them have lapsed, usually after about 12 to 15 years. At that point, other companies can make and sell the drugs. Generics are much less expensive than newer brand-name medicines, but they are not lesser quality drugs. Indeed, most generics remain useful medicines even many years after first being marketed. That is why more than 75 percent of all prescriptions in the U.S. today are written for generics.
4. Keep up-to-date records.
Another important issue to talk with your doctor about is keeping a record of the drugs you take. There are several reasons for this:
- First, if you see several doctors, each may not be aware of medicines the others have prescribed.
- Second, since people differ in their response to medications, it's common for doctors today to prescribe several medicines before finding one that works well or best.
- Third, many people take several prescription medications, nonprescription drugs, and dietary supplements at the same time. They can interact in ways that can either reduce the benefit you get from the drug or be dangerous.
- Fourth, the names of prescription drugs-both generic and brand-are often hard to pronounce and remember.
For all these reasons, it's important to keep a written list of all the drugs and supplements you take and periodically review it with your doctors.
5. Know the facts.
Finally, always be sure that you understand the dose of the medicine being prescribed and how many pills you are expected to take each day. Your doctor should tell you this information. When you fill a prescription at a pharmacy, or if you get it by mail, check to see that the dose and the number of pills per day on the bottle match the amounts your doctor told you.
How We Picked the Best Buy Antidepressants
Our evaluation is based on scientific reviews of the evidence on the effectiveness, safety, and adverse effects of antidepressants conducted by Oregon Health & Science University's Drug Effectiveness Review Project, or DERP, and the Agency for Healthcare Research and Quality, or AHRQ, and an updated search of studies published through October 2012. DERP is a first-of-its-kind multi-state initiative to evaluate the comparative effectiveness and safety of hundreds of prescription drugs.
A synopsis of DERP's and AHRQ's analyses of antidepressants forms the basis for this report. A consultant to Consumer Reports Best Buy Drugs is also a member of the Oregon-based research team, which has no financial interest in any pharmaceutical company or product.
The full DERP review of antidepressants is available at: http://derp.ohsu.edu/about/final-document-display. cfm (It is a long and technical document written for physicians and experts.) The AHRQ review is available at: http://www.ncbi.nlm.nih.gov/books/NBK83442/.
The drug costs we cite were obtained from a healthcare information company that tracks the sales of prescription drugs in the U.S. Prices for a drug can vary quite widely, even within a single city or town. The prices in this report are national averages based on sales of prescription drugs in retail outlets. They reflect the "cash" or retail price paid for a month's supply of each drug in May 2013. As noted in the Antidepressant Cost Comparison table, some antidepressants are available through discount generic drug programs run by chain stores. However, these programs can change which medications are covered, so those prices are not used when selecting the Best Buy picks.
Consumer Reports Best Buy Drugs selected the Best Buy Drugs using the following criteria. The drug (and dose) had to:
- Be in the top tier of effectiveness among antidepressants.
- Have a safety and side-effect record equal to or better than other antidepressants.
- Have an average price for a 30-day supply that was substantially lower than the most costly antidepressant meeting the first two criteria.
The Consumer Reports Best Buy Drugs methodology is described in more detail in the methods section at www.CRBestBuyDrugs.org.
Sharing This Report
This copyrighted report can be downloaded free, reprinted, and disseminated for individual noncommercial use without permission from Consumers Union or Consumer Reports® magazine as long as it is clearly attributed to Consumer Reports Best Buy Drugs™. We encourage its wide dissemination as well for the purpose of informing consumers. But Consumers Union does not authorize the use of its name or materials for commercial, marketing, or promotional purposes. Any organization interested in broader distribution of this report should email email@example.com. Consumer Reports Best Buy Drugs™ is a trademarked property of Consumers Union. All quotes from the material should cite Consumer Reports Best Buy Drugs™ as the source.
2013 Consumers Union of U.S., Inc.
Consumer Reports is an independent and nonprofit organization whose mission since 1936 has been to provide consumers with unbiased information on goods and services and to create a fair marketplace. Its website is www.ConsumerReports.org.
Consumer Reports Best Buy Drugs is a publiceducation project administered by Consumers Union. These materials were made possible by the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by a multistate settlement of consumer-fraud claims regarding the marketing of the prescription drug Neurontin.
The Engelberg foundation provided a major grant to fund the creation of the project from 2004 to 2007. Additional initial funding came from the National Library of Medicine, part of the National Institutes of Health. A more detailed explanation of the project is available at www.CRBestBuyDrugs.org.
We followed a rigorous editorial process to ensure that the information in this report and on the Consumer Reports Best Buy Drugs website is accurate and describes generally accepted clinical practices. If we find an error or are alerted to one, we will correct it as quickly as possible. But Consumer Reports and its authors, editors, publishers, licensers, and suppliers cannot be responsible for medical errors or omissions, or any consequences from the use of the information on this site. Please refer to our user agreement at www.CRBestBuyDrugs.org for further information.
Consumer Reports Best Buy Drugs should not be viewed as a substitute for a consultation with a medical or health professional. This report and the information on www.CRBestBuyDrugs.org are provided to enhance your communication with your doctor rather than to replace it.
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Antidepressant Cost Comparison
Note: If the price box contains a , that indicates the dose of that drug is likely available for a low monthly cost through discount programs offered by large chain stores. For example, Kroger, Sam's Club, Target, and Walmart offer a month's supply of selected generic drugs for $4 or a three-month supply for $10. Other chain stores, such as Costco, CVS, Kmart, and Walgreens, offer similar programs. Some programs have restrictions or membership fees, so check the details carefully for restrictions and to make sure your drug is covered.
Narrow your list
|Generic Name and Strength||Brand NameA||Frequency of UseB||Average Monthly CostC|
|Bupropion 75 mg tablet||Wellbutrin||Three a day||$289|
|1||Bupropion 75 mg tablet||Generic||Three a day||$64|
|Bupropion 100 mg tablet||Wellbutrin||Three a day||$357|
|1||Bupropion 100 mg tablet||Generic||Three a day||$80|
|Bupropion 100 mg sustained-release tablet||Wellbutrin SR||Two a day||$280|
|Bupropion 100 mg sustained-release tablet||Budeprion SR||Two a day||$104|
|Bupropion 100 mg sustained-release tablet||Generic||Two a day||$62|
|Bupropion 150 mg extended-release tablet||Wellbutrin XL||One a day||$276|
|Bupropion 150 mg extended-release tablet||Budeprion XL||One a day||$158|
|Bupropion 150 mg extended-release tablet||Generic||One a day||$80|
|Bupropion 150 mg sustained-release tablet||Wellbutrin SR||Two a day||$294|
|Bupropion 150 mg sustained-release tablet||Budeprion SR||Two a day||$99|
|Bupropion 150 mg sustained-release tablet||Generic||Two a day||$63|
|Bupropion 200 mg sustained-release tablet||Wellbutrin SR||Two a day||$541|
|Bupropion 200 mg sustained-release tablet||Generic||Two a day||$140|
|Bupropion 300 mg extended-release tablet||Wellbutrin XL||One a day||$406|
|Bupropion 300 mg extended-release tablet||Budeprion XL||One a day||$141|
|Bupropion 300 mg extended-release tablet||Generic||One a day||$81|
|Bupropion 174 mg extended-release tablet||Aplenzin||One a day||$339|
|Bupropion 348 mg extended-release tablet||Aplenzin||One a day||$468|
|Bupropion 522 mg extended-release tablet||Aplenzin||One a day||$1,053|
|Citalopram 10 mg tablet||Celexa||One a day||$179|
|1||Citalopram 10 mg tablet||Generic||One a day||$32|
|Citalopram 20 mg tablet||Celexa||One a day||$192|
|1||Citalopram 20 mg tablet||Generic||One a day||$25|
|Citalopram 40 mg tablet||Celexa||One a day||$195|
|1||Citalopram 40 mg tablet||Generic||One a day||$33|
|Citalopram 10 mg/5 mL oral solution||Generic||One dose per day||$61|
|Desvenlafaxine 50 mg sustained-release tablet||Pristiq||One a day||$196|
|Desvenlafaxine 100 mg sustained-release tabletD||Pristiq||One a day||$203|
|Duloxetine 20 mg capsule||Cymbalta||One a day||$226|
|Duloxetine 30 mg capsule||Cymbalta||One a day||$244|
|Duloxetine 60 mg capsule||Cymbalta||One a day||$247|
|Escitalopram 5 mg tablet||Lexapro||One a day||$193|
|1||Escitalopram 5 mg tablet||Generic||One a day||$86|
|Escitalopram 10 mg tablet||Lexapro||One a day||$171|
|1||Escitalopram 10 mg tablet||Generic||One a day||$87|
|Escitalopram 20 mg tablet||Lexapro||One a day||$183|
|1||Escitalopram 20 mg tablet||Generic||One a day||$88|
|Escitalopram 5 mg/5 mL oral solution||Generic||One dose per day||$121|
|Fluoxetine 10 mg capsule||Prozac||One a day||$257|
|1||Fluoxetine 10 mg capsule||Generic||One a day||$28|
|1||Fluoxetine 10 mg tablet||Generic||One a day||$49|
|Fluoxetine 20 mg capsule||Prozac||One a day||$260|
|1||Fluoxetine 20 mg capsule||Generic||One a day||$31|
|1||Fluoxetine 20 mg tablet||Generic||One a day||$31|
|Fluoxetine 40 mg capsule||Prozac||One a day||$535|
|1||Fluoxetine 40 mg capsule||Generic||One a day||$99|
|1||Fluoxetine 60 mg tablet||Generic||One a day||$94|
|Fluoxetine 90 mg delayed-release capsule||Prozac Weekly||One per week||$199|
|Fluoxetine 90 mg delayed-release capsule||Generic||One per week||$145|
|Fluoxetine 20 mg/5 mL oral solution||Generic||One dose per day||$80|
|Fluvoxamine 100 mg tablet||Generic||One a day||$45|
|Fluvoxamine 100 mg continuous-delivery capsule||Luvox CR||One a day||$463|
|Fluvoxamine 100 mg continuous-delivery capsule||Generic||One a day||$302|
|Fluvoxamine 150 mg continuous-delivery capsule||Luvox CR||One a day||$417|
|Fluvoxamine 150 mg continuous-delivery capsule||Generic||One a day||$316|
|Mirtazapine 7.5 mg tablet||Generic||One at bedtime||$69|
|Mirtazapine 15 mg tablet||Remeron||One at bedtime||$169|
|Mirtazapine 15 mg tablet||Generic||One at bedtime||$44|
|Mirtazapine 15 mg dissolvable tablet||Generic||One at bedtime||$63|
|Mirtazapine 30 mg tablet||Remeron||One at bedtime||$170|
|Mirtazapine 30 mg tablet||Generic||One at bedtime||$42|
|Mirtazapine 30 mg dissolvable tablet||Remeron||One at bedtime||$150|
|Mirtazapine 30 mg dissolvable tablet||Generic||One at bedtime||$70|
|Mirtazapine 45 mg tablet||Generic||One at bedtime||$42|
|Mirtazapine 45 mg dissolvable tablet||Generic||One at bedtime||$72|
|Paroxetine 10 mg tablet||Paxil||One a day||$144|
|Paroxetine 10 mg tablet||Pexeva||One a day||$260|
|Paroxetine 10 mg tablet||Generic||One a day||$21|
|Paroxetine 20 mg tablet||Paxil||One a day||$160|
|Paroxetine 20 mg tablet||Pexeva||One a day||$253|
|Paroxetine 20 mg tablet||Generic||One a day||$21|
|Paroxetine 30 mg tablet||Paxil||One a day||$171|
|Paroxetine 30 mg tablet||Pexeva||One a day||$263|
|Paroxetine 30 mg tablet||Generic||One a day||$38|
|Paroxetine 40 mg tablet||Paxil||One a day||$170|
|Paroxetine 40 mg tablet||Pexeva||One a day||$331|
|Paroxetine 40 mg tablet||Generic||One a day||$37|
|Paroxetine 12.5 mg sustained-release tablet||Paxil CR||One a day||$153|
|Paroxetine 12.5 mg sustained-release tablet||Generic||One a day||$94|
|Paroxetine 25 mg sustained-release tablet||Paxil CR||One a day||$168|
|Paroxetine 25 mg sustained-release tablet||Generic||One a day||$103|
|Paroxetine 37.5 mg sustained-release tablet||Paxil CR||One a day||$177|
|Paroxetine 37.5 mg sustained-release tablet||Generic||One a day||$110|
|Paroxetine 10 mg/5 mL oral suspension||Paxil||One dose per day||$151|
|Sertraline 25 mg tablet||Zoloft||One a day||$185|
|1||Sertraline 25 mg tablet||Generic||One a day||$33|
|Sertraline 50 mg tablet||Zoloft||One a day||$174|
|1||Sertraline 50 mg tablet||Generic||One a day||$29|
|Sertraline 100 mg tablet||Zoloft||One a day||$181|
|1||Sertraline 100 mg tablet||Generic||One a day||$33|
|Sertraline 20 mg/mL oral suspension||Generic||One a day||$159|
|Venlafaxine 25 mg tablet||Generic||Two a day||$89|
|Venlafaxine 37.5 mg tablet||Generic||Two a day||$83|
|Venlafaxine 50 mg tablet||Generic||Two a day||$93|
|Venlafaxine 75 mg tablet||Generic||Two a day||$78|
|Venlafaxine 100 mg tablet||Generic||Two a day||$99|
|Venlafaxine 37.5 mg sustained-release tablet||Generic||One a day||$119|
|Venlafaxine 75 mg sustained-release tablet||Generic||One a day||$108|
|Venlafaxine 150 mg sustained-release tablet||Generic||One a day||$120|
|Venlafaxine 225 mg sustained-release tablet||Generic||One a day||$270|
|Venlafaxine 37.5 mg continuous-delivery capsule||Effexor XR||One a day||$209|
|Venlafaxine 37.5 mg continuous-delivery capsule||Generic||One a day||$90|
|Venlafaxine 75 mg continuous-delivery capsule||Effexor XR||One a day||$223|
|Venlafaxine 75 mg continuous-delivery capsule||Generic||One a day||$100|
|Venlafaxine 150 mg continuous-delivery capsule||Effexor XR||One a day||$218|
|Venlafaxine 150 mg continuous-delivery capsule||Generic||One a day||$105|
- "Generic" indicates drug sold by generic name
- As typically prescribed.
- Prices reflect nationwide retail average for May 2013, rounded to the nearest dollar. Information derived by Consumer Reports Best Buy Drugs from data provided by Symphony Health Solutions, which is not involved in our analysis or recommendations.
- According to Pristiq's drug label, "in clinical studies, doses of 50-400 mg/day were shown to be effective, although no additional benefit was demonstrated at doses greater than 50 mg/day and adverse events and discontinuations were more frequent at higher doses."