Back in the 1950s, scientists doing studies on the old-school antidepressants reserpine and isoniazid found that these drugs changed neuro-transmitter activity—and that in the majority of patients, they eased symptoms of depression. This led to a theory that a biochemical imbalance—specifically, an imbalance of neurotransmitters—was responsible for depression. This neat, tidy theory created an absolutely massive market for drugs designed to manipulate neuro-transmitter levels. The theory lasted for half a century, and the huge market for drugs that affect the reuptake of serotonin and other neuro-transmitters promises to long outlive it. But as the saying goes, the most beautiful theories are often slain by facts, and this theory was no exception. The truth, according to psychiatrist and director of the North Wales School of Psychological Medicine, David Healy, M.D., is that “no abnormality of serotonin in depression has ever been demonstrated.”
In the world of psychiatry and psychiatric research, no one is talking about these chemical imbalances anymore. The real death-knell of this theory is the fact that the newest antidepressants, Cymbalta, Serzone, and Effexor, inhibit the reuptake not only of serotonin, but also of another neurotransmitter, norepinephrine. The drugs belong to a new class, the serotonin-norepinephrine reuptake inhibitors (SNRIs). Everything old is new again, including the idea that the best antidepressants are not highly specific magic bullets designed to correct an “imbalance” in a single neurotransmitter, but are those that have broader effects. (Natural therapies for depression and anxiety have broad effects as well.)
Neurotransmitter levels are responsive to your emotional state. If anyone ever does establish physical differences in neurotransmitter activity between depressed or anxious people and healthy people, they’ll then face another daunting challenge: unraveling whether any changes in neurotransmitter levels or other kinds of brain activity that are found in depressed people are a cause or an effect of depression or anxiety. Neurotransmitters are active throughout our bodies in many, many ways, and when we alter their activity with drugs, we’re entering territory that is far from completely mapped. John Horgan, in his book The Undiscovered Mind, writes, “Given the ubiquity of a neurotransmitter such as serotonin and the multiplicity of its functions, it is almost as meaningless to implicate it in depression as it is to implicate blood.”
The risks of popular antidepressants make headlines often, with shocking revelations that drug companies have actively sought to suppress the public’s knowledge of side effects (including suicidality, loss of libido and sexual function, severe withdrawal effects that convince the patient that he or she has to get back on the medications, and akathisia, a restlessness that can be severe enough to make the patient violent or suicidal).
Akathisia, which involves extreme restlessness, jitteriness, anxiety, and inability to sit still, is a major issue with all SSRIs. Prozac, the original, has been found to induce akathisia in between 9.7 and 25 percent of patients (this according to a review performed at Harvard University). In its labeling for Paxil, Glaxo-SmithKline intentionally avoided the use of this term, choosing instead to describe the symptoms of akathisia as various other side effects—spreading the incidence out to reduce the appearance of akathisia as a significant issue with this drug. This would have enabled them to market their product as less likely to cause anxiety and jitteriness than other SSRIs. Akathisia can swoop in very quickly on a patient in the first three days of taking SSRIs, even at the lowest dose. Antidepressants now have to carry black-box warnings of increased risk of suicidal and violent behavior in those who use them. If you take antidepressants or have a loved one who makes this choice, please know that they all can increase risk of suicidal thinking or suicide attempts. This is more true in people under the age of 24.
The black-box warnings for these drugs state that “[a]ll patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.” Antidepressant information sheets for prescribing doctors also warn that
. . . anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Not only are antidepressants less safe than people are led to believe; they are also less effective than most people know. A team that used the Freedom of Information Act to access both published and unpublished studies on SSRI effectiveness found that these drugs were only barely more effective than placebo. A study published in the January 17, 2008, issue of the New England Journal of Medicine reinforces this question mark. The study’s authors found that while 94 percent of antidepressant studies published in medical journals had positive results (i.e., the drug had more beneficial effects than placebo pills on people with depression), only 51 percent of studies on antidepressants in the FDA’s registry had positive results. In other words, the studies published in medical journals have not given an accurate picture of the effectiveness of antidepressant drugs. If you do try an antidepressant, don’t be surprised if it doesn’t work or if you try two or three different versions before you find one with the desired effect. If you take the drugs for a long time, don’t be surprised if they become ineffective. At that point, you may find yourself being prescribed ever-higher doses of medication or even having drugs added to the mix. This is not a scientific practice, folks. In doing this kind of trial-and-error prescribing, psychiatry is conducting a massive, uncontrolled experiment on millions of people’s brains. Don’t go there unless absolutely necessary.
Today, anxiety is often treated with the same kinds of drugs used to treat depression. The benzodiazepines (such as Ativan, Xanax, Halcion) and other tranquilizers that once were commonly prescribed for anxiety are addictive and produce too many side effects for long-term use, including drowsiness, memory impairment, and poor coordination. Withdrawal from these drugs can cause psychosis, insomnia, even seizures. In some cases, these antianxiety drugs become the cause of anxiety that just happens to manifest in a person who is using them to treat depression. Anxiety is a known side effect of antianxiety drugs, just as depression is a known side effect of the antidepressants.
In the short term, if a person is in great distress and needs fast help, these prescription drugs may be the lesser evils—even though they are not always effective and may make things worse. But they are not long-term solutions, and for many people who are not in extreme states of anxiety or depression, they may not be necessary at all. So if we are to turn away from the pharmaceutical fix-it for depression and anxiety, what do we turn to? This is the question we would like to begin to answer in the latter half of this chapter.
First, let’s look at the most-prescribed sleeping pills, antidepressants, and antianxiety drugs. If you do choose to take them, please educate yourself well about side effects, potential for abuse, and potential for addiction. Please remember they are not lightweight drugs. None has been proven safe for long-term use (more than two years), and many have been essentially banned for use by children 12 and under.
Of particular concern is the effect of anti-anxiety drugs and sleep-inducing drugs on drivers. According to an organization called Citizens Against Drug-Impaired Drivers (CANDID), prescription and over-the-counter medications that cause drowsiness contribute to more than 100,000 car crashes a year. If your drug insert warns against driving while under the influence of the drug, please take that warning seriously!
Examples of Prescription Drugs for Sleep
Z
olpidem tartrate (Ambien, Ambien CR)
What Does It Do in the Body? This drug has a hypnotic, sedative, muscle relaxant effect, which it achieves by altering neurotransmitter channels in the brain. CR stands for “controlled release,” a version of the drug that has longer-lasting effects.
What Is It Used For? To aid sleep.
What Are the Potential Side Effects? In clinical trials of this drug, 4 to 6 percent of subjects stopped taking Ambien because they were so bothered by side effects. The most common is headache. Others include drowsiness, dizziness, lethargy, a “drugged” feeling, light-headedness, depression, abnormal dreams, amnesia, anxiety, nervousness, sleep disorder, allergy, back pain, flulike symptoms, chest pain, fatigue, nausea, stomach upset, diarrhea, abdominal pain, constipation, loss of appetite, vomiting, muscle pain, upper respiratory infection, sinus and throat inflammation, runny nose, rash, urinary tract infection, palpitations, and dry mouth. Dozens of other side effects may occur, but they are more rare.
CAUTION!
Ambien should be used only for 7 to 10 days at a time. Insomnia may at its root be caused by an underlying physical or psychiatric disorder, and if you need to use drugs to get to sleep for more than a week to 10 days, you should look deeper and try to solve the problem. Other import ant tips:
• Be sure to use the smallest effective dose of this drug.
• If you have breathing problems such as asthma or emphysema, use sedatives with caution, as they can depress the body’s instinctual drive to breathe.
• If you have been addicted to any drug, you should know that zolpidem tartrate can be addictive.
• Any sedative or hypnotic drug can cause abnormal thinking and behavioral changes much like those caused by alcohol. Decreased inhibition and increased aggression, bizarre behavior, hallucinations, feelings of unreality, and amnesia could be attributed to taking this drug.
• If you are suffering from depression, this drug may make it worse and even precipitate suicidal thinking.
• Abrupt discontinuation of Ambien can lead to withdrawal symptoms ranging from a mild downshift in mood and insomnia to abdominal or muscle cramps, vomiting, sweating, tremors, and convulsions.
• This drug has a very rapid onset of action, so only take it right before going to bed. It may affect your ability to drive or operate machinery, even the following day, so use caution.
• Those with impaired liver function should use this drug with caution if at all.
• If you are elderly or debilitated, you may have heightened sensitivity to this drug, and you should be monitored carefully.
Be Aware. Do not combine Ambien with alcohol or narcotics.
Zaleplon (Sonata)
What Does It Do in the Body? It affects neuro-transmitter channels in the brain, bringing on sleepiness and relaxation, and relieving anxiety. Its mechanism of action is similar to that of Ambien, but it is a faster-acting drug.
What Is It Used For? A sleep aid.
What Are the Potential Side Effects? Three-and-a-half percent of subjects who took Sonata in clinical trials discontinued the drug because of adverse effects. The most common included migraine, depression, nervousness, difficulty
Sleep Aids Associated with Strange Sleep Behaviors
In 2007, the FDA released a warning about the danger of sleepwalking, sleep-eating, sleep-driving, and other complex behaviors occurring in people under the influence of the following sleep drugs:
Ambien/Ambien CR
Lunesta
Rozerem
Sonata
Butisol sodium
Carbrital
Seconal (barbiturates; rarely prescribed)
Dalmane
Doral
Halcion
Prosom
Restoril (benzodiazepines)
Placidyl (a highly addictive and rarely prescribed sleep medicine)
These behaviors are more likely in people who use other medications or drink alcohol after taking the sleep drug. The FDA also warns that the drugs in this list have significant risk of causing a severe allergic reaction.
concentrating, rash, itching, constipation, dry mouth, exacerbation of arthritis symptoms, bronchitis, conjunctivitis, back pain, and chest pain. Higher doses were more likely to bring about adverse effects.
CAUTION!
Insomnia should not be treated with Sonata for more than 7 to 10 days. This drug can cause changes in thinking and behavior, including uncharacteristic aggression, extroversion, agitation, and hallucinations. Sudden stopping of the drug can cause symptoms of withdrawal; talk to your doctor about tapering off if you must use this drug. Take Sonata only right before bed, and be aware that it could affect your coordination and alertness in the morning.
Be Aware. Never mix zaleplon with alcohol or narcotics. If taken with a heavy, high-fat meal, the drug’s absorption may be delayed. The drug rifampin can decrease zaleplon’s effectiveness, and cimetidine increases it.
Sleep Problems Can Be a Result of Other Conditions
All of the hypnotic sleep drugs carry a warning in their prescribing information about the possibility that difficulty sleeping could be a symptom of some other health problem that needs to be addressed. Doctors are directed to thoroughly evaluate patients with sleep problems before prescribing these drugs, to make sure that no other physical or psychological issue needs to be addressed to heal the insomnia. Some people who were enrolled as subjects in studies of these kinds of drugs had worsening insomnia or other thought or behavior abnormalities emerge during drug treatment.
Keep in mind, however, that the use of a consciousness-altering medication could easily be the cause of these seemingly new abnormalities. This is a common issue with psychiatric drugs: the patient goes to the doctor with a psychiatric complaint, gets on a medication, and then has some other “previously masked” psychiatric complaint “emerge” while on the drug. No one really knows whether the drug is unmasking these previously masked conditions—or causing them.
Eszopiclone (Lunesta)
What Does It Do in the Body? No one is quite sure how eszopiclone works to bring on sleep. It is believed to work via effects on receptors for the relaxant neurotransmitter GABA.
What Is It Used For? A sleep aid.
What Are the Potential Side Effects? The most common complaint with this drug is an unpleasant taste in the mouth, which affected about one-third of those taking the highest dose and about one-fourth of those taking the lower dose in preapproval studies. Other side effects are memory impairment, sleepiness, headache, infection, dry mouth, upset stomach, vomiting, anxiety, confusion, depression, dizziness, hallucinations, decreased libido, nervousness, and rash.
CAUTION!
Insomnia should not be treated with Lunesta for more than 7 to 10 days. This drug can cause changes in thinking and behavior, including uncharacteristic aggression, extroversion, agitation, a feeling of detachment, amnesia, and worsening of pre-existing depression or suicidal thinking. There have been reports of withdrawal symptoms after several weeks of use, leading to symptoms such as anxiety, abnormal dreams, intense sensitivity to stimuli, or neurosis. Talk to your doctor about tapering off if you must use this drug. Only take Lunesta right before bed, and be aware that it could affect your coordination and alertness in the morning.
Be Aware. Never mix eszopiclone with alcohol or narcotics. If taken with a heavy, high-fat meal, the drug’s absorption may be delayed. The drug olanzapine can interact to increase cognitive impairment when taken with eszopiclone, and rifampin can decrease its effectiveness.
Ramelteon (Rozerem)
What Does It Do in the Body? It affects receptors for the hormone melatonin, which is produced in the brain and brings on sleep.
What Is It Used For? To aid sleep in people with insomnia characterized by difficulty falling asleep (as opposed to difficulty staying asleep). Unlike other sleep drugs, Rozerem has not been found to have risks of rebound insomnia, addiction, or withdrawal symptoms.
What Are the Potent
ial Side Effects? Sleepiness, fatigue, dizziness, nausea, worsening insomnia, upper respiratory tract infection, muscle pain, depression, distortion of sense of taste, joint pain, flu, increased blood cortisol levels.
Galactorrhea (milk production) in non-nursing women, cessation of menstrual periods, decreased libido, or reduced fertility can indicate an effect of ramelteon on levels of the hormones prolactin and testosterone.
CAUTION!
Think Twice About Taking This Drug If . . .
• You have been diagnosed with sleep apnea or chronic obstructive pulmonary disease (COPD).
• You are depressed or have had suicidal thoughts. Ramelteon has been associated with worsening of both depression and suicidal thinking.
• You have kidney impairment.
Be Aware. Ramelteon should not be taken with fluvoxamine (Luvox). Taking ramelteon with or just after a high-fat meal may reduce the drug’s effectiveness.
Examples of Nonprescription Antihistamine Sleep Aids
Diphenhydramine (Benadryl, Dormin Caplets, Miles Nervine Caplets, Nytol, Sleep-Eze 3, Sleepwell 2-nite, Sominex 2, Extra Strength Tylenol PM, Aspirin Free Anacin P.M. Caplets, Bayer Select Maximum Strength Night Time Pain Relief Caplets, Sominex Pain Relief, Bufferin AF Nite Time Caplets, Excedrin P.M., Unisom with Pain Relief, Compoz Nighttime Sleep Aid, Sominex Caplets, Twilite, Compoz Gel Caps, Dormin, Maximum Strength Sleepinal Capsules and Soft Gels, Maximum Strength Unisom SleepGels, Nighttime Pamprin)
Prescription Alternatives Page 39