Common popularly prescribed antidepressants are associated with weight gain when taken long term. (14, 62, 113, 122, 124, 762, 763, 2174-2177, 2206, 2192)
17.9% of people who take the most popular antidepressants, in the SSRI family gained greater than 7% weight (medically significant weight gain). (149) A more recent study found 40.6% of people taking antidepressant drugs for 6 to 36 months gained more than 7% body weight compared to their baseline weight. (2206)
A large study in Finland of 151,347 working women and men reported the risk of developing type 2 diabetes doubled if a person took more than 200 doses of antidepressant medications. People who had no signs of severe depression had a 1.9X increased risk of developing diabetes if they took more than 200 doses of antidepressant. People with signs of severe depression and who took more than 200 doses of antidepressant had a 3.17X increased risk of developing diabetes compared to people who did not have depression and who were not taking a drug for depression. Antidepressant users also gained weight (p<0.0001). (2192)
Two of three people with major depression arrive for therapy with weight loss. Gaining weight often accompanies successful therapy. “Weight gain is of concern—and likely to be drug-induced—if it exceeds the depression-induced weight loss and continues after depressive symptoms improve.” Schwartz, TL et at, 2007, Current Psychiatry (58)
After Kristin started on Prozac antidepressant medication she stopped sleeping 20 hours per day. However, with the increased dose of antidepressant, she developed the opposite problem—she couldn’t sleep. The levels of serotonin in her brain increased because she was taking the Prozac SSRI. Serotonin has a side effect of making it difficult to sleep.
Kristin’s psychiatrist prescribed Xanax (alprazolam) sleep medication to help her sleep and said it would relieve anxiety as well. Xanax (alprazolam) is in the popular benzodiazepine (benzo) family and is similar and acts similar to a sister family of drugs, the cyclopyrrolones (or imidazopyridine “Z drugs”) family, which includes Ambien and Lunesta. Both benzos and cyclopyrrolones/imidazopyridine “Z” drugs are used to help with insomnia to help people sleep.
The first famous benzo was Valium (diazepam). Valium is also used to treat anxiety and as a muscle relaxant. Valium was the first drug sold in the benzo family and at one time was the number one selling drug in the U.S. Xanax (alprazolam), Klonopin (clonazepam) and Ativan (lorazepam) are other popular examples of benzos.
Principal Question 1:
SSRI antidepressants frequently cause sleeplessness. What are
the side effects and risks of the most common sleep medications?
Is there an alternative to taking sleep medications?
Kristin, her parents, and her winter sports coach were concerned about her using Xanax (alprazolam) for sleep. The drug slows physical reaction times even days and years after the drug is taken. Kristin’s skeleton racing required lightning-fast reflexes as she traveled about 80 miles per hour downhill on ice. Any reduction in reflexes and reaction speed could spell serious injury or even death.
Medical journals have published articles on slowed reaction times in people taking the benzodiazepine drugs. Driving after taking benzos has resulted in auto accidents. The car accident rate is increased for years even after people stop taking the medication.
The Lancet
Reported: Users of benzodiazepines (benzos) and zopiclone (a cyclopyrrolone similar to benzos) were at increased risk of experiencing a road-traffic accident (757).
One reason is that this family of drugs is fat soluble, and the brain is 50% fat; so, these drugs tend to hang around in the brain. Benzos can then leach out of the fat unexpectedly in the future and influence reaction times. People who have taken the drugs have fallen asleep at the wheel of their cars even after not taking the drug for quite some time. Kristin’s parents were concerned the Xanax (alprazolam) could leach out later under stress during a skeleton race or when she was driving on long trips with the sports team and cause her to have an accident.
Kristin elected not to take the sleep medication and to “see how it goes.”
The increased amount of Prozac began to further relieve Kristin’s depression slowly over time. She became happier and was doing better according to her family.
However, Kristin was still “Sleepless in Seattle.”
In 2012, a large study of over 34 thousand people taking benzos or “Z drugs” linked these medications with increased and premature death higher than in people who do not take the drugs. (756) Over a 7-year period there were 4 excess deaths per 100 people followed if they took benzodiazepines or “Z drugs” zolpidem (Ambien, Edluar, Intermezzo), zopiclone, eszopiclone (Lunesta), zaleplon (Sonata) of the cyclopyrrolone family for sleep.
The death rate was increased even if a person took only 18 benzo (benzodiazepine) pills or “Z drug” pills per year. This large study of people being seen in the United Kingdom (UK) for primary care, showed anxiety and sleep (hypnotic) benzo drugs were associated with a significantly increased risk of death over a seven-year period. Scott W, et al, British Medical Journal BMJ 2014. (756) These BMJ (British Medical Journal) findings are consistent with previous evidence of a statistically and clinically significant association between anti-anxiety and sleep-aid prescription drugs and death (mortality) Lancet (757). Here is what was already known about benzodiazepines:
Benzodiazepine anxiety relieving and sleep aid drugs are psychologically addictive. They are associated with thinking (cognitive) and physical coordination (psychomotor) impairments, falls, and unintentional injuries.
Doctors and health care workers long been suspected that these benzo sleep and anxiety drugs are associated with premature death.
Studies of the association between anxiety and sleep drugs and premature death have reported varying result rates and have used a variety of methods to collect data. (757)
What the large study by Scott W, et al published in the BMJ (British Medical Journal) (757) revealed:
In this large group of people being cared for in UK primary care clinics, anxiety and sleep benzo drugs were associated with a significantly increased risk of mortality over a seven-year period.
After excluding deaths in the first year, there were about 4 (four) excess deaths linked to benzo drugs use per 100 people followed for an average of 7.6 years after their first prescription. (757)
Benzodiazepine sleep medications are being reported in the news to kill half a million people per year.
The reason for the deaths is not certain, but theories include auto accidents, falls, worsening of sleep apnea, and depression. In September 2020 the FDA issued new Special Safety Alerts for benzodiazepines.
The FDA required an update to the “Black Box Warning” to include the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions to help improve their safe use. The FDA also required other changes to the Warnings and Precautions, Drug Abuse and Dependence, and Patient Counseling Information sections of the prescribing information for all benzodiazepine products. Further, the FDA is requiring revisions to the patient Medication Guides for these drugs to help educate patients and caregivers about these risks. There is also an alert about the dangers of taking benzodiazepines in combination with pain medications especially opioid narcotics.
“ALERT: US Boxed Warning
Risk from concomitant use with opioids:
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.”
Commonly prescribed newer sleep medications include “Z drugs” Ambien (zolpidem) and Lunesta (eszopiclone). They are in the imidazopyridine and cyclopyrrolone families of drugs. They are a sister family of benzodiazepines and work very similarly to benzodiazepines. Similar increases in driving accidents as those reported for benzo users are reported for people who take Ambien and Lunesta.
Benzodiazepine sleep medications are generally not effective with long-term use and work for only about 1 to 2 months before tolerance and psychological addiction to the drugs may develop. Cognitive and behavioral therapy to teach how to improve sleep are the proven therapy for sleeplessness.
Usually using the lowest effective dose of SSRI antidepressant allows for adequate sleep when combined with behavioral therapy and practicing routine good sleep hygiene.
Benzodiazepine (“Benzo”) and imidazopyridine drugs are depressant drugs and are known as “downers” because they work by reducing the number of nerve impulses in the brain and spinal cord. The depressant effect of Xanax (alprazolam) can undo some of the antidepressant effect of Prozac (fluoxetine).
The Xanax (alprazolam) sleep medication is also potentially psychologically addicting. The benzodiazepine family of drugs can be rapidly addicting psychologically, and many people have trouble giving up their sleep and anti-anxiety drugs.
Withdrawal from Xanax (alprazolam) and benzodiazepines / imidazopyridines can result in deep depression. This withdrawal depression may last from 1 month to several months. For Kristin, who was already diagnosed with depression and was barely coping with it, the additional and prolonged depression she could suffer while coming off Xanax (alprazolam) posed a potentially serious problem.
In the first 6 months of Prozac SSRI therapy Kristin lost 2 pounds, though she was not overweight before starting the SSRI antidepressant.
In the second 6 months of taking Prozac, Kristin gained 9 pounds. Her pants did not fit; she was upset, frustrated, and desperate about her appearance. Everyone in her family was an athlete, and her mom raised the family on organic home cooked foods only. Her mom did not usually serve sweets, and when she did make dessert, she cooked according to her European roots and health orientation. She tended to make healthy rich French desserts that are low in sugar. Kristin was the only person in the family who was taking on weight. She craved starchy carbohydrates (carbs) like pasta, rice, bread, sweets. Increased carbohydrate (carb) craving and changes in histamine levels, which control appetite in the brain, are typical with SSRI antidepressants. While health food was served at home, Kristin was tempted at her part-time job, where fancy catered food and desserts were always available. The initial weight gain added speed to her downhill skeleton racing, but any further gains, she knew, would be fat not muscle.
Muscles control reaction times and turning ability for athletes—whether the athletes are skeleton racers, downhill skiers, boarders, or football players being tested in the NFL agility run. Fat slows reactions in sports and inhibits turning and agility. Fat is dead weight in sports.
Two Hormone Paths Contribute to SSRI Antidepressant Weight Gain:
Serotonin typically reduces food intake and helps regulate appetite and carbohydrate intake and is the most often manipulated neurotransmitter in depression treatment.
SSRI drugs (Selective Serotonin Reuptake Inhibitors) increase food intake and craving for carbohydrates (carbs). Initially this unexpected side effect of SSRI antidepressants was considered a “paradox” by researchers. (2178)
However, SSRI family antidepressant drugs were found to decrease histamine levels which causes increase in appetite (58).
Principal Question 2:
What is the pattern of weight loss and weight gain with drugs like Prozac (fluoxetine) in the SSRI family used for treating depression?
The usual pattern for weight changes with SSRI antidepressant medications is mild weight loss for the first two to six months. Many people are very happy with this initial effect. However, they come to realize that after 2-6 months, the SSRI family of drugs usually causes a slight increase in appetite, especially for sweets and starchy carbohydrates, and then typically continual gradual weight gain can occur for as long as the drug is taken.
Initial weight loss is followed by long-term weight gain. A controlled long-term study lasting 47 weeks showed a 7% or more weight gain after starting Prozac (fluoxetine) in 17.9% of people taking the drug (149).
Is a weight gain of 7% above a person’s previous weight a big deal? Medical literature indicates that a gain of 5% or more weight impacts health negatively. The FDA officially states that 7% weight gain negatively impacts health. Weight gains of 5% or more increase risk of diabetes, heart disease, depression, cancer, high blood pressure, osteoarthritis, and other illnesses. Gaining weight is a big health risk.
Another long-term study showed an average weight gain of 6.82 pounds in 50 weeks in people taking Prozac (fluoxetine) (58).
Prozac may have a different effect on weight if a person is already obese. In people who were obese before they start taking Prozac (fluoxetine), one study that lasted for 1 year showed a slight loss of weight, but the weight loss was not significant when compared to the other group of people who were given placebo (no drug) instead of Prozac. (704)
Weight gain can complicate a person’s depression. Especially in teenage girls and women, unwanted weight gain can be frustrating and depressing. SSRIs are associated with carbohydrate (carb) craving; thus, the resulting weight gain tends to be fat not muscle.
Frustrated with the weight gain and lack of sleep, Kristin stopped taking her Prozac without telling her doctor or her parents.
Within days she experienced the side effects of sudden SSRI antidepressant Prozac withdrawal. Antidepressant drugs in the SSRI family are supposed to be withdrawn slowly by reducing the dose by small amounts over time to prevent withdrawal symptoms. Kristin was depressed and felt physically ill, and her thoughts of suicide returned. She missed winter sports practice and a big race.
Kristin finally told her parents she had stopped the Prozac (fluoxetine). She realized she needed the drug, at least for now, and let her parents take her back to the doctor and help her explain her problem with the drug. Her doctor wanted her to continue with Prozac because she had responded well, and he told her the weight gain had to be something that took second precedence.
To find out how Kristin attempts to deal with the weight gain and lack of sleep after restarting her Prozac antidepressant please read Blog 4 about Depression.
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Not recognizing that marijuana has similar slowing effects on sports reaction times as the “benzo” sleep medication she had previously been prescribed by her doctor, Kristin accepted the offer from her friend. She began to smoke the marijuana before bedtime, either outside the family home or in her car on the way home from work. At first it seemed to help her sleep. But the marijuana was not consistent. Plus, she started to like it and began using it frequently-almost nightly.