If you develop a rash within hours of starting a new medicine, you don’t need Sherlock Holmes to help you make the connection. Some drug side effects are harder to identify.
Psychological reactions can be especially insidious, appearing slowly over weeks or even months. Distinguishing between the normal ups and downs of life and a drug-induced depression can be difficult. If a prescriber does not warn a patient or her family about psychiatric side effects, the outcome could be disastrous.
Drug-Induced Depression–A Challenging Side Effect:
Depression is a devastating disorder. It can rob people of their motivation, appetite, sex drive, concentration, sleep and energy. Relationships suffer. Major depressive disorder sucks the joy out of life.
When depression strikes spontaneously, it can be challenging to treat. If it occurs as a side effect of medication, diagnosis can be difficult and treating it can be even more problematic.
Healthcare professionals don’t always warn their patients that psychological depression can be an adverse drug reaction. But hundreds of medications may impact mood.
Reserpine and Depression:
One of the earliest connections between prescribed medicine and depressive symptoms involves a blood pressure medication called reserpine. It was derived from a plant called Rauwolfia serpentina and was widely used after its FDA approval in 1955. More recently, however, it has fallen out of favor because of numerous side effects, including psychological depression.
Drug companies and the FDA are sometimes slow to recognize this adverse reaction. That’s in part because it may take weeks or months for depressive symptoms to show up. At first, they may be subtle. A clinical trial that only lasts several weeks may not reveal unexpected psychiatric drug side effects.
Reglan: A Drug for Heartburn:
When Sylvia was put on a heartburn medicine called metoclopramide (Reglan), she never expected to experience psychiatric side effects or a psychotic breakdown. After all, how could something for your stomach affect your brain?
Yet Sylvia was in and out of a mental hospital during the time she was on metoclopramide because she experienced hallucinations, depression, confusion and anxiety.
She wondered whether any of her medicines might be contributing to her problems but her psychiatrist didn’t think that was likely. Little did he know that the metoclopramide that was prescribed for her GI tract can cause psychiatric symptoms such as severe depression and hallucinations, confusion, anxiety, seizures, insomnia, involuntary muscle contractions and restlessness.
Another reader shared this reaction to Reglan:
“I was stopped at an intersection on an icy day waiting for a sand truck to pass when I almost pulled out in front of him–intentionally.
“When I saw the young man’s face, I said to myself, ‘I cannot do this to him.’ After the truck passed and I drove on, I wondered what in the world was going on. I was not depressed.
“When I arrived home, I was still shaken from what I had almost done. I read the daily newspaper while I ate lunch. The first article in your column that day was from a lady whose husband had committed suicide while taking Reglan.
“That was the exact same medication my doctor had prescribed for my stomach. I jumped up and emptied that bottle down the toilet and wrote on it in large letters, DO NOT TAKE AGAIN. I thank God and the lady who wrote you that letter.”
Reglan (metoclopramide) carries a warning that it can cause mental depression and suicidal ideation. Patients should always be cautioned about such a serious complication.
Sometimes a medicine is essential, and any psychological reactions it causes can be handled with another medication.
Could an Antihistamine Spark Suicidal Thoughts?
Q. My dermatologist recommended I take Xyzal for eczema because it was not supposed to make me sleepy the way Zyrtec did. I found Xyzal made me just as sleepy and very depressed after just a low dose.
I can’t find depression listed as a side effect. However, I get so depressed that I’m frightened to take it anymore. Have you heard of this side effect for either Xyzal or Zyrtec?
A. The generic name for Zyrtec is cetirizine. The generic name for Xyzal is levocetirizine. That means they share a very similar chemical structure.
Both drugs are considered non-drowsy antihistamines. In theory, Xyzal is supposed to be a little less likely to cause sedation than Zyrtec. On the other hand, drowsiness is listed as one of the most common reactions, along with sore throat, fatigue and dry mouth.
We were surprised to discover that suicidal ideation has been reported as a reaction to Xyzal. In addition, a review of medications associated with depression included cetirizine (JAMA, June 12, 2018). There are a number of other ways to treat eczema. You may want to ask your dermatologist about alternate approaches.
Unexpected Psychiatric Side Effects:
People are not surprised when a medication prescribed for anxiety, ADHD, depression or psychosis causes emotional ups and downs. That’s also true for hallucinogens! Remember the famous song, White Rabbit, sung by Grace Slick and Jefferson Airplane:
“One pill makes you larger, and one pill makes you small
And the ones that mother gives you, don’t do anything at all
Go ask Alice, when she’s ten feet tall…”
If you have not listened to White Rabbit in awhile, please scroll up and click on the link. It is a memorable performance that is worth a moment of your time.
Antibiotics and Hallucinations?
Stories of hallucinations associated with LSD or “magic mushrooms” do not surprise health professionals or patients. What surprises people are stories about antibiotics and hallucinations:
Linda was put on an antibacterial drug called ofloxacin (Floxin) for a routine urinary tract infection. She took her medicine for granted, expecting a rapid cure with few, if any, side effects. In the past, antibiotics had caused some stomach upset and mild diarrhea.
Ofloxacin was different. Insomnia, anxiety, visual disruption, paranoid thoughts and hallucinations panicked Linda. She was diagnosed with toxic psychosis.
Simvastatin and Drug-Induced Depression
Like Sylvia and Linda, most people are unprepared for psychiatric reactions to everyday medicines. We heard from one bereaved daughter whose father committed suicide after taking the cholesterol-lowering drug simvastatin for a few years.
She wrote:
“Prior to that he had never been depressed. I have since met a patient who can directly attribute the start of depression with beginning on simvastatin and its end with stopping the drug.”
We suspect it will come as a surprise to most cardiologists to see “depression” listed as a “Nervous System Disorder” under the category of Postmarketing Experience for Zocor (simvastatin).
To be fair, some studies suggest that statins actually reduce symptoms of depression. But here is one article that seems to confirm a risk of psychiatric side effects associated with statins (Drug Safety Case Reports, Dec. 2016).
The authors introduce their case series this way:
“Most adverse drug reaction (ADR) reporting focuses on non-behavioral health risks to the medication-taking individual; however, attention is increasingly given to drug-induced behavioral and mood changes that may affect self or others. Drugs and medications with behavioral concerns include alcohol (best recognized), but also varenicline, loratadine, mefloquine, tramadol, isotretinoin, tricyclics, benzodiazepines, and selective serotonin reuptake inhibitors (SSRIs), among others. Emerging evidence suggests such problems may occasionally arise with cholesterol-lowering drugs.”
They report the results of their study:
“Behavioral and psychiatric changes in the cases presented range from violent nightmares to aggression, mood/personality change, violent or homicidal ideation (in some instances culminating in suicide), each in apparent association with statin use. The temporal association between the drug initiation and mood and behavior change, and again between drug discontinuation and resolution of symptoms where this occurred, suggests a causal connection in a number of these cases.”
The Beta Blocker Blues:
Another reader described her downward spiral after starting hormone replacement therapy. The migraines that resulted led to a prescription for a beta blocker called propranolol.
Within months she found herself severely depressed and barely able to function. When the hormones were discontinued, her migraines stopped. Without headaches or beta blocker medication, the depression lifted.
Corticosteroids and Psychiatric Drug Side Effects:
Prednisone and other corticosteroids are frequently prescribed to ease severe allergic reactions or sinusitis. A bad case of poison ivy often merits a substantial dose of oral steroid. Commonly, a doctor will prescribe a big starting dose that tapers down over the next week or two or three.
Big doses of prednisone, even for just a few days, can trigger some strange reactions, including anxiety, emotional lability, irritability, insomnia, depression, agitation, distractibility, memory impairment, auditory and visual hallucinations and other delusions. There is even a name for this condition: “steroid psychosis.”
Prozac and Suicidal Ideation:
Also, people resist the idea that a drug intended to make patients feel better could have such a negative impact on their lives. We too were slow to recognize the possibility that the antidepressant fluoxetine (Prozac) could trigger suicidal thoughts.
This drug was first approved by the FDA in 1987. A physician wrote to us shortly thereafter to tell us about the tragic suicide of his daughter. Initially, we could not believe an antidepressant could trigger suicidal thoughts. But by 1990 psychiatrists from Harvard published six case reports of people who developed “intense violent suicidal preoccupations after 2-7 weeks of fluoxetine treatment” (American Journal of Psychiatry, Feb. 1990).
Our interactions with the maker of Prozac and the FDA left much to be desired. Both organizations denied there could be a connection. Today, fluoxetine and many other antidepressants carry a prominent warning in their prescribing information about suicidal thoughts and behaviors.
Weight Loss Drugs and Depression?
There are many other medicines that may cause depression as a side effect, but those designed to affect appetite deserve special scrutiny. In the mid-2000s, a drug called rimonabant was approved in Europe. It blocked cannabinoid receptors and helped people lose weight.
However, in 2007 the FDA decided not to approve it because the agency was not convinced it was safe. That turned out to be a smart move. By 2009, rimonabant had been pulled off the global market because of serious psychiatric side effects, including suicide.
Semaglutide: Ozempic and Wegovy?
Might this be a problem for the hottest drugs in the pharmacy today? Semaglutide is the active pharmaceutical ingredient in three different drugs: Ozempic, Rybelsus and Wegovy. Doctors prescribe the first two to help control blood sugar in people with type 2 diabetes. Wegovy is indicated to help people lose weight.
Is depression an adverse effect of semaglutide? There are some case reports, but there is no mention of psychiatric reactions in the prescribing information for either Ozempic or Rybelsus.
The Wegovy information cautions doctors:
“Monitor patients treated with WEGOVY for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.”
Patients should discuss such reactions with their healthcare providers, who may consider changing the treatment plan.
Anticholinergic Drugs, Memory Loss and Confusion:
Here is another improbable connection. The bladder seems remote from the brain and drugs to treat so-called overactive bladder appear totally unrelated to mental clarity.
This reader shared a story that may be far more common than most people realize:
“I am a 49-year-old female who has been on oxybutynin (Ditropan) for a few years. I had my family doctor refer me to a psychiatrist because I was having much more trouble remembering things.
“On my first visit to the specialist, I gave her a list of all the medications I was on. (I was taking six medications and had to write them down, as I could never remember them.) As soon as she saw the oxybutynin, she told me that confusion is a side effect.
“I never even tied the two together. The bladder and the head are rather far apart! I immediately stopped taking the Ditropan and felt much better right away. I was attributing my depression and confusion to menopause. It worries me that there could be thousands of people suffering and not making the connection.”
If you would like a list of other anticholinergic drugs that you would never suspect could cause confusion or memory problems, here is a link.
Health Professionals and Psychiatric Side Effects:
Many physicians do not warn patients about psychiatric side effects. We have heard from many people who got a big dose of prednisone for a skin problem but they were not warned about irritability, insomnia or other unpleasant emotional complications. When someone reports anxiety, depression or insomnia, doctors may assume the problem lies with the patient’s coping skills or life circumstances.
This faulty thinking is sometimes extended to patients having trouble getting off anxiety medicines such as lorezepam (Ativan) or alprazolam (Xanax) or antidepressants like venlafaxine (Effexor), paroxetine (Paxil) and sertraline (Zoloft). Some physicians believe withdrawal difficulties are caused by a return of the patient’s initial psychological complaints.
One woman was distressed that her doctor did not take her symptoms of dizziness, bizarre dreams, headaches, sensory disturbances and anxiety seriously. Although he had heard of paroxetine withdrawal, he thought only “troubled” or seriously depressed patients had such problems, and she didn’t fit that category.
Tramadol and Psychiatric Side Effects:
Now that doctors are wary 0f prescribing opioid pain relievers like hydrocodone or oxycodone, they are turning to drugs like tramadol. They may not realize that this pain reliever can cause hallucinations (see this link). Stopping tramadol can also trigger brain zaps, tremors, nightmares, depression and hallucinations. Here is a link to over 500 stories about tramadol.
Learn More:
To discover the large number of medications that can cause unexpected and potentially serious mental changes, why not download our free Guide to Psychological Side Effects?
Physicians and patients must recognize that symptoms ranging from depression or disorientation to anxiety and hallucinations might be due to medication. Certain antibiotics, cholesterol-lowering drugs, pain relievers and steroids such as prednisone are just a few of the commonly prescribed drugs that can trigger psychiatric side effects.
Share your own story below so others can benefit from your experience.
