Robert F. Kennedy Jr, now head of HHS, recently said that antidepressant medicines are addictive and as hard to quit as heroin. As usual, this is misinformation and is not true. In this post I am going to write about the epidemiology of major depression, the subtypes of major depression and treatment options.
Unipolar Major Depression
This is the most common type of major depression. In the US 20% of adults (1 in 5) will have at least one episode of unipolar major depression at some time in their lives. The prevalence in any one year is about 8%. People who have one episode of depression have a 70% likelihood of have a recurrent episode of depression.
This is a bad disease and it can kill. To make the diagnosis symptoms must include at least five of the following:
- Sadness or irritability, lasting most of the day
- Loss of interest in the majority of activities that were enjoyable before
- Change in appetite, or sudden weight loss/gain
- Difficulty falling asleep, or wanting to sleep more than before
- Feelings of restlessness
- Lack of energy and increased tiredness
- Feelings of worthlessness or guilt, often linking to things that normally wouldn’t have this kind of effect
- Difficulty concentrating, making decisions and thinking
- Suicidal or self-harming thoughts
Two to eight percent of people with unipolar major depression commit suicide.
Major depression is not a disease just of modern times. Abraham Lincoln had severe depressions, which he called “melancholy.” Winston Churchill also had severe depressions. He called it the “black dog.” The famous author William Styron, who wrote Sophie’s Choice and The Confessions of Nat Turner also had bad depressions. He wrote a book about his experience of depression called Darkness Visible. It is worth reading in order to understand how depression is felt.
Risk factors for unipolar depression
There is a genetic component. Unipolar depression tends to run in families. Other risk factors include social isolation, chronic stress, history of psychological trauma, unresolved grief or loss and substance abuse.
Treatment of unipolar major depression
Medicines
When I first went into practice the only antidepressant medicines we had was a class of medicines called tricyclic antidepressants. Examples include amitriptyline and imipramine.These were actually quite effective, better than the medicines we use today, but tricyclics had a major problem. They were very dangerous in overdose. They could cause lethal cardiac arrhythmias that were difficult or impossible to treat.
We almost never use the tricyclics anymore because of the overdose danger. The medicines we use now are called SSRI’s (serotonin re-uptake inhibitors) or SNRI’s (serotonin and norepinephrine re-uptake inhibitors). The first of SSRI was fluoxetine (Prozac). Others in this class include sertraline (Zoloft), citalopram (Celexa) and paroxetine (Paxil). SNRI’s include things like venlaxafine (Effexor) and duloxetine (Cymbalta). The SSRI’s and SNRI’s are not quite as effective as the tricyclics, but are much safer. An overdose can be unpleasant, but it will not kill you.
How well do SSRI’s and SNRI’s work?
Clinical trials of antidepressants show a large placebo effect, up to 35% in adults and up to 40% in adolescents. That means that a little over 1/3 of people have improvement of their symptoms of depression taking only a placebo. The placebo effect is real. People actually measurably get better. It is not just that they just think they are getting better. The response to antidepressants in these trials show a response rate of about 50%. Thus overall the effectiveness of antidepressants in these trials is modest. In practice, however, we find that most people respond well to antidepressants although some do not. The difference may well be that people who respond well are getting medicine effect plus a context effect that comes from having a relationship with a trusted physician who prescribes the medicine. A good relationship with a trusted physician can promote healing in addition to medicines.
What about Kennedy’s claim that they are addictive? Addiction is a chronic disease that involves compusive use of a substance or engagement in an activity despite harmful consequences. It can be physical or psychological. SSRI’s and NSRI’s do not cause compulsive use or generate any craving for the drug, so they do not meet the definition of being addictive.
What about his claim that they are harder to get off of than heroin? About 20% of people who suddenly stop an SSRI or NSRI have unpleasant symptoms called antidepressant discontinuation syndrome. It is more likely to happen to people on high doses or who have been on antidepressants for a long time. Symptoms are usually mild and last for a week or two. Symptoms can include flu-like symptoms, nausea, trouble sleeping and anxiety. Tapering the antidepressant slowly usually prevents this syndrome, but a few people still get it and it can rarely be severe. It is least likely to happen with long acting antidepressants like Prozac and more likely to happen with short acting antidepressants like Paxil and Zoloft. It is nothing like withdrawal from heroin, which usually requires medication assistance with suboxone or methadone to successfully treat the addiction.
Psychotherapy
Many kinds of psychotherapy work for depression. The most commonly used psychotherapy for depression is cognitive behavioral therapy (CBT). It has been compared to antidepressants in multiple studies and has been found to be just as effective (but not more effective) than antidepressant medicines. Interestingly, studies where both antidepressant medicine and CBT are used together are not more effective than either used alone.
The problem with CBT is not its effectiveness, but its availability. It is time consuming, expensive, and insurance sometimes does not pay for it. There are not nearly enough CBT practitioners to treat everyone suffering from major depression.
Other Treatments for Unipolar Depression
Electroshock therapy
This is an old treatment but it is still used for severe depression that is resistant to other treatments. Techniques have been improved so that there are no permanent brain changes from electroshock treatment.
Stimulation of the vagus nerve
Some studies have shown that stimulation of the vagus nerve can reduce symptoms of unipolar depression.
Psilocybin
There was a very promising randomized trial of a single dose of the hallucinogen psilocybin given with psychological support. It produced marked improvement in unipolar depression that persisted for at least 43 days, which was as long as the subjects were followed. There were no adverse effects. Here is a link to that paper in the Journal of the American Medical Association (JAMA): Single-Dose Psilocybin Treatment for Major Depressive Disorder
Bipolar Disorder
Bipolar 1 disorder
This used to be called manic-depressive illness. It is characterized by episodes of mania. People with mania have markedly elevated mood, and feelings of euphoria and invincibility. They sleep very little, have rapid pressured speech, and often have very inappropriate behavior, including sexual impulsivity and other impulsive behaviors. They may purchase things they can’t afford. These manic episodes may last for days or weeks, but are followed by episodes of severe depression. Bipolar 1 disorder has a different neurochemical basis than unipolar depression. It has a very strong genetic component. There is no one gene for bipolar 1 disorder. Many genes are thought to be involved. Bipolar disorder of either type is much less common than unipolar depression. Only about 4% of people will have bipolar disorder in their lifetime.
Bipolar 2 disorder.
Bipolar 2 disorder is very similar to bipolar 1 disorder but less severe. People with bipolar 2 disorder can have fairly long episodes of normal functioning between episodes.
Treatment of Bipolar Disorder
Treatment of bipolar disorder always involves medicines. Antidepressants can be used for the depressive phase, but are usually avoided because they can precipitate mania. The most common medicine used for bipolar disorder is lithium. Lithium prevents both manic and depressive phases in bipolar disorder. Other medicines can be used but those are specialized anti-psychotic medicines that are beyond the scope of this review.
Bottom Line
Unipolar depression is common, causes significant disability and can lead to suicide. Antidepressant medicines are effective treatments for most but not all people with unipolar depression. Psychotherapy, especially cognitive behavioral therapy works as well as medicines in the treatment of unipolar depression. SSRI’s and SNRI’s are not addictive. Sudden stopping of antidepressant medicines can lead to unpleasant symptoms in about 20% of patients. These symptoms are usually mild and last about 2 weeks. They can almost always be prevented by tapering down the medicines over the course of a couple of weeks. Bipolar disorder is much less common, is primarily genetic, and is treated with different medicines from unipolar depression.