Antidepressants

Is depression caused by a chemical imbalance in the brain?

You’ve seen it in television ads, read it in newspaper articles, maybe even heard it from your doctor: depression is caused by a chemical imbalance in the brain that medication can correct. According to the chemical imbalance theory, low levels of the brain chemical serotonin lead to depression and depression medication works by bringing serotonin levels back to normal. However, the truth is that researchers know very little about how antidepressants work. There is no test that can measure the amount of serotonin in the living brain – no way to even know what a low or normal level of serotonin is, let alone show that depression medication fixes these levels.

While antidepressant drugs such as Prozac increase serotonin levels in the brain, this doesn’t mean that depression is caused by a serotonin shortage. After all, aspirin may cure a headache, but it doesn’t mean that headaches are caused by an aspirin deficiency. Furthermore, many studies contradict the chemical imbalance theory of depression. Experiments have shown that lowering people’s serotonin levels doesn’t always lower mood, nor does it worsen symptoms in people who are already depressed. And while antidepressants raise serotonin levels within hours, it takes weeks before medication kicks in to relieve depression. If depression were due to low serotonin, there wouldn’t be an antidepressant medication lag.

How effective are antidepressants?

Researchers agree that when depression is severe, medication can be helpful – even life saving. However,research shows that antidepressants fall short for many people. A major government study released in 2006 showed that less than 50 percent of people become symptom-free on antidepressants, even after trying two different medications. Furthermore, many who do respond to medication slip back into major depression within a short while, despite sticking with drug treatment.

Other studies show that the benefits of depression medication have been exaggerated – with some researchers concluding that, when it comes to mild to moderate depression, antidepressants are only slightly more effective than placebos.

If you have severe depression that’s interfering with your ability to function, medication may be right for you. However, many people use antidepressants when therapy, exercise, or self-help strategies would work just as well or better – minus the side effects. Therapy can also help you get to the bottom of your underlying issues and develop the tools to beat depression for good.

Side effects of antidepressant medication

The types of drugs used in the treatment of depression are selective serotonin reuptake inhibitors (SSRIs), “atypical” antidepressants, and the older  tricyclic antidepressants, and monoamine oxidase inhibitors (MAOIs). Side effects are common in all antidepressants and for many people, the side effects are serious enough to make them stop taking the medication.

Side effects of SSRIs (selective serotonin reuptake inhibitors)

The most widely prescribed antidepressants come from a class of medications known as selective serotonin reuptake inhibitors (SSRIs).

The SSRIs include:

• Fluoxetine (Prozac)
• Fluvoxamine (Luvox)
• Sertraline (Zoloft)
• Paroxetine (Paxil)
• Escitalopram (Lexapro)
• Citalopram (Celexa)

The SSRIs act on a chemical in the brain called serotonin. Serotonin helps regulate  mood, but it also plays a role in digestion, pain, sleep, mental clarity, and other bodily functions. As a result, the SSRI antidepressants cause a wide range of side effects.

Common side effects include sexual problems, drowsiness, sleep difficulties, and nausea. While some side effects go away after the first few weeks of drug treatment, others persist and may even get worse.

In adults over the age of 65, SSRIs pose an additional concern. Studies show that SSRI medications may increase the risk for falls, fractures, and bone loss in older adults. The SSRIs can also cause serious withdrawal symptoms if you stop taking them abruptly.

Side effects of atypical antidepressants

There are a variety of newer depression drugs, called atypical antidepressants, which target other neurotransmitters either alone or in addition to serotonin. Some of the brain chemicals they affect include norepinephrine and dopamine.

The side effects vary according to the specific drug. However, many of the atypical antidepressants can cause nausea, fatigue, weight gain, sleepiness, nervousness, dry mouth, and blurred vision.

The atypical antidepressants include:

Bupropion (Wellbutrin) Venlafaxine (Effexor) Duloxetine (Cymbalta)

Mirtazapine (Remeron) Trazodone (Desyrel) Nefazodone (Serzone)

Side effects of older depression drugs

Tricyclic antidepressants and MAOIs (monoamine oxidase inhibitors) are older classes of antidepressants. Their side effects are more severe than those of the newer antidepressants, so they are only prescribed as a last resort after other treatments and medications have failed.

Antidepressant withdrawal

Once you’ve started taking antidepressants, stopping can be tough; many people have withdrawal symptoms that make it difficult to get off of the medication.

If you decide to stop taking antidepressants, it’s essential to taper off slowly. If you stop abruptly, you may experience a number of unpleasant withdrawal symptoms such as crying spells, extreme restlessness, dizziness, fatigue, and aches and pains. These withdrawal symptoms are known as antidepressant discontinuation syndrome. Antidepressant discontinuation syndrome is especially common when you stop taking Paxil or Zoloft. However, all medications for depression can cause withdrawal symptoms.

Depression and anxiety are also common symptoms when withdrawing from antidepressants. When depression is a withdrawal symptom, it’s often worse than the original depression that led to drug treatment in the first place. Unfortunately, many people mistake this withdrawal symptom for a return of their depressive illness and resume medication, creating a vicious circle.

In order to avoid antidepressant withdrawal symptoms, never stop your medication “cold turkey.” Instead, gradually taper your dose, allowing for at least 1-2 weeks between each dosage reduction. This tapering process may take up to several months, and should be monitored under a doctor's supervision.

Antidepressants and suicide risk

There is a danger that, in some people, antidepressant treatment will cause an increase, rather than a decrease, in depression. In fact, the U.S. Food and Drug Administration requires that all depression medications include a warning label about the increased risk of suicide in children and young adults. The suicide risk is particularly great during the first month to two months of treatment.

Anyone taking antidepressants should be closely watched for suicidal thoughts and behaviors. Monitoring is especially important if this is the person’s first time on depression medication or if the dose has recently been changed. Signs that medication is making things worse include anxiety, insomnia, hostility, and extreme agitation—particularly if the symptoms appear suddenly or rapidly deteriorate. If you spot the warning signs in yourself or a loved one, contact your doctor or therapist immediately.

Exploring your depression treatment options

Antidepressants aren’t a cure. Medication may treat some symptoms of depression, but can’t change underlying contributions to depression in your life. Antidepressants won’t solve your problems if you’re depressed because of a dead-end job, a pessimistic outlook, or an unhealthy relationship. That’s where therapy and other lifestyle changes come in.

Studies show that therapy works just as well as antidepressants in treating depression, and it’s better at preventing relapse once treatment ends. While depression medication only helps as long as you’re taking it, the emotional insights and coping skills acquired during therapy can have a more lasting effect on depression. However, if your depression is so severe that you don't have the energy to pursue treatment, a brief trial of antidepressants may boost your mood to a level where you can focus on therapy.

In addition to therapy, other effective treatments for depression include exercise, meditation, relaxation techniques, stress management, support groups, and self-help steps. While these treatments require more time and effort initially, their advantage over depression medication is that they boost mood without any adverse effects

Deciding if depression medication is right for you

If you’re considering antidepressants as a treatment option, make sure you carefully consider all of your treatment options. The following questions may help you make your decision.

Questions to ask yourself and a mental health professional

• Is my depression severe enough to justify drug treatment?
• Is medication the best option for treating my depression?
• Am I willing to tolerate unwanted side effects?
• What non-drug treatments might help my depression?
• Do I have the time and motivation to pursue other treatments such as therapy and exercise?
• What self-help strategies might reduce my depression?
• If I decide to take medication, should I pursue therapy as well?

Questions to ask your doctor

• Are there any medical conditions that could be causing my depression?
• What are the side effects and risks of the antidepressant you are recommending?
• Are there any foods or other substances I will need to avoid?
• How will this drug interact with other prescriptions I’m taking?
• How long will I have to take this medication?
• Will withdrawing from the drug be difficult?
• Will my depression return when I stop taking medication?

If you use antidepressants

If you decide to take depression medication, it’s prudent to learn all you can about your prescription.  The more you know about your antidepressant, the better equipped you’ll be to deal with side effects, avoid dangerous drug interactions, and minimize other safety concerns.

Some suggestions:

• See a psychiatrist, not a family physician. Your family physician might help you or your loved one first realize that you may need depression treatment. But although any medical doctor can prescribe medications, psychiatrists are doctors who specialize in mental health treatment. They are more likely to be familiar with the newest research on antidepressants and any safety concerns. Your health depends on your doctor's expertise, so it's important to choose the physician who is best qualified.
• Be patient. Finding the right drug and dosage is a trial and error process. It takes approximately 4 to 6 weeks for antidepressant medications to reach their full therapeutic effect. Many people try several medications before finding one that helps.
• Monitor side effects – Keep track of any physical and emotional changes you’re experiencing and talk to your doctor about them. Contact your doctor or therapist immediately if your depression gets worse or you experience an increase in suicidal thoughts.
• Don’t stop medication without talking to your doctor – Be sure to take your antidepressant according to the doctor's instructions. Don't skip or alter your dose, and don't stop taking your pills as soon as you begin to feel better. Stopping treatment prematurely is associated with high relapse rates. It can also cause serious withdrawal symptoms.
• Go to therapy – Medication can reduce the symptoms of depression, but it doesn’t treat the underlying problem. Psychotherapy can help you get to the root of your depression, change negative thinking patterns, and learn new ways of coping.

Related links for antidepressant medication

General information about depression medication

You and Your Antidepressant – Covers antidepressant side effects, medication do’s and don’ts, and advice on depression medication treatment goals. (McMan's Depression and Bipolar Web)

Weighing the Ups and Downs of Taking Antidepressants – Learn how antidepressants work, what their benefits and risks are, and what to expect when taking them. (Health.com)

Antidepressants: Comparing Effectiveness, Safety, Side Effects, and Price (PDF) – Report helps consumers assess whether antidepressants are right for them, and if so, which one. (Consumer Reports)

Psychiatry by Prescription – Article on the growing use of psychotropic medications, including antidepressants, for relatively mild conditions. (Harvard Magazine)

CDC: Antidepressants most prescribed drugs in U.S. – News report on the rise of antidepressant prescriptions and their overuse in many adults. (CNN)

How antidepressants work

Head Fake – Article on the misguided theory that low serotonin is responsible for depression, and new research that points to the real way antidepressants work. (Boston Globe)

The Anatomy of Mood: Biology and the Brain – Covers new evidence that antidepressants help depression by promoting neurogenesis and brain growth. (The Johns Hopkins Depression and Anxiety Bulletin)

Depression: Beyond Serotonin – Explains that depression is much more than just a chemical imbalance, and that it involves the whole brain and body. (Psychology Today)

Some Drugs Work to Treat Depression, But It Isn't Clear How – Reviews the lack of evidence for the chemical imbalance theory of depression. Includes new theories on how antidepressants work. (Wall Street Journal)

Antidepressant side effects and risks

Clinical Trials - What the Drug Companies Don't Report – Desribes the placebo effect in antidepressants and the high dropout rate due to side effects. (McMan's Depression and Bipolar Web)

Suicidality in Children and Adolescents Being Treated With Antidepressant Medications – FDA Public Health Advisory on the increased suicide risk in children and adolescents taking antidepressants. (U.S. Food and Drug Administration)

Sexual Problems and Depression – Learn about the sexual side effects of antidepressants and how to treat the problem. (Cleveland Clinic)

Antidepressant Use Linked to Bone Loss – Covers two Archives of Internal Medicine studies on the connection between SSRI use in adults over 65 and abnormal bone loss. (National Institutes of Health)

How to Take an Antidepressant – A guide to depression drugs that includes a discussion on the two “especially bothersome” side effects: sexual dysfunction and weight gain. (Psychology Today)

Antidepressant treatment guidelines

Antidepressants: Selecting One That's Right for You – Introduction to the various types of antidepressants and how to find the right one for you. (Mayo Clinic)

How To Think About Medication – Tips on recognizing when antidepressants are appropriate and how to take charge of your health and drug treatment. (Psychology Today)

Why Settle for Silver, When You Can Go for Gold? Response vs. Recovery as the Goal of Antidepressant Therapy – Emphasizes the importance of attaining full remission when treating depression, rather than just a reduction in symptoms. (Brainstorms)

Antidepressant withdrawal

Getting Off Antidepressants: Antidepressant Discontinuation Syndrome – Learn about antidepressant withdrawal and how to stop taking an SSRI drug safely. (HealthyPlace)

Dependence on Antidepressants & Halting SSRIs – Advice from a doctor on how to withdraw from SSRI medication without experiencing adverse symptoms. (Benzodiazepine Addiction, Withdrawal & Recovery)

Antidepressant Discontinuation Syndrome – Written for doctors, this journal article covers the withdrawal symptoms of abrupt SSRI discontinuation. (American Family Physician)

Paxil Withdrawal Guide (PDF) – In-depth guide covers how to stop taking Paxil, a selective serotonin reuptake inhibitor, while minimizing withdrawal symptoms. (Darcy Baston)

Melinda Smith, M.A., and Jeanne Segal, Ph.D., contributed to this article. Last modified: August 08.