# The Ongoing Search for Safe Alternatives to Anxiety Medications
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A recent piece in Quillette argues that simply switching alcoholics to other medications could effectively treat alcoholism. The drugs in question are non-benzodiazepine anticonvulsants (NBACs), which were originally developed to address seizures and epilepsy. Among these, the author lists several specific medications: baclofen, carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide. Baclofen, gabapentin, and topiramate are highlighted as the most researched for alleviating post-withdrawal symptoms.
These medications are characterized as non-addictive because they do not produce euphoria, meaning patients don't feel "high" while taking them. Additionally, users do not develop a tolerance, so they don’t need increasing doses to achieve the same effects. When effective, NBACs simply alleviate symptoms, restoring normal sleep, appetite, and mood. As a result, users often find themselves indifferent to alcohol, leading to sustained sobriety without significant effort.
However, I have reservations about this perspective. For instance, my aunt relies on gabapentin nightly for sleep. She has attempted to stop taking it multiple times but has failed each time, ultimately resigning herself to lifelong use. This experience makes me skeptical of the claim that these medications are truly "non-addictive."
Insomnia is prevalent in my family, and I've battled it myself for years, experimenting with various sleep aids over a decade. I became addicted to one and had to stop using all sleeping pills. I tried gabapentin briefly and found it altered my state; while it wasn’t euphoric, I felt distinctly sedated. Online discussions reveal that many individuals misuse gabapentin, and others develop tolerance, requiring higher doses over time.
I managed to discontinue gabapentin, but experienced withdrawal symptoms. Quitting the drug suddenly poses the risk of seizures, necessitating a gradual tapering over several months. Even after stopping, withdrawal effects can linger for months. The Quillette author suggests gabapentin can ease long-term withdrawal symptoms from alcohol, but it can lead to tolerance and prolonged withdrawal when discontinued.
There’s a fundamental flaw in the argument presented. While it may be true that the listed medications might be safer than alcohol, labeling any of them as genuinely safe is questionable. History also casts doubt on this assertion. For decades, researchers have sought a perfect tranquilizer devoid of addiction and withdrawal symptoms. Every decade, pharmaceutical companies unveil a new product marketed as safe, only for it to prove just as problematic as its predecessors. There’s a clear pattern here.
Before delving deeper, let’s examine the history of sedatives.
The Original Sedative: Alcohol
Historically, drug discoveries were often accidental. In ancient times, someone likely consumed fermented food and noticed its effects, leading to the production of mead, wine, beer, and spirits.
The social context surrounding alcohol is vast and complex, but I will focus on its neurochemical aspects. The brain contains GABA (gamma-aminobutyric acid), which inhibits neurotransmission, and glutamate, which has the opposite effect. Normal brain function relies on a balance between these two chemicals.
Alcohol is a multifaceted substance, primarily enhancing GABA and suppressing glutamate. This effect slows brain function, leading to decreased coordination and cognitive impairment, along with sedation.
Hangovers are complex as well; they result from a combination of self-poisoning and neurochemical imbalances. Following alcohol consumption, the brain compensates by producing more glutamate, which can make sounds seem louder and lights too bright. Sleep patterns are often disrupted, leading to early awakenings after a night of drinking.
Interestingly, some individuals find that consuming more alcohol the next morning temporarily alleviates hangover symptoms. If this behavior continues daily, the brain adjusts, anticipating the drug's presence.
When an alcoholic stops drinking, their brain is thrown into turmoil; neurons expect the calming effects of alcohol, which are absent. As glutamate levels surge, withdrawal symptoms can include anxiety, tremors, restlessness, vomiting, and more severe manifestations like delirium tremens, characterized by extreme agitation and hallucinations. In some cases, withdrawal can lead to seizures or even death.
The Introduction of Barbiturates
In 1903, German chemists discovered that a compound known as barbital could effectively sedate dogs. The Bayer company commercialized this discovery, prompting the development of numerous related compounds. This marked the availability of non-alcoholic sedatives.
Barbiturates function similarly to alcohol by amplifying GABA's effects in the brain. While they may be cleaner than alcohol—resulting in less cognitive impairment—they still pose a significant risk of dependence. Withdrawal from barbiturates mirrors that of alcohol, with sudden cessation potentially leading to seizures or death.
Initially, the dangers of addiction and dependence were overlooked. Barbiturates were marketed as safe coping mechanisms, particularly for women.
The Rise of Miltown in the 1950s
Miltown emerged from another lab accident in 1948. A researcher searching for a penicillin preservative stumbled upon mephenesin, which calmed lab rats. While this drug had limitations, further research led to the development of meprobamate, which addressed these issues. By 1955, it was marketed as Miltown and became a massive success, accounting for a third of all prescriptions written by 1957.
Miltown was initially recommended for alcoholics but was primarily consumed by everyday individuals under stress. Advertisements targeted women, suggesting the drug was beneficial for parenting.
As time went on, it became evident that Miltown led to both physical and psychological dependence. Quitting abruptly could result in life-threatening symptoms akin to those seen with alcohol and barbiturates.
The mechanism of action for Miltown is similar to other sedatives; it binds to GABA receptors, slowing neuron transmission. Some sedatives enhance natural GABA's effects, while Miltown can function independently of it, making it perilous when combined with other sedatives or alcohol.
My grandmother was among those who relied on Miltown, a habit my father recalls vividly: "Your grandmother lived on Miltown as far back as I can remember. Certainly bipolar. She took them with scotch."
The Emergence of Valium
Benzodiazepines followed as the next category of "safe" sedatives, with Librium being discovered accidentally in 1960 and Valium in 1963.
Valium was marketed to various demographics, including single women and older women suffering from hypochondria. It was even advertised as beneficial for men feeling overwhelmed by women.
While benzodiazepines present a lower overdose risk compared to barbiturates and are generally less toxic to brain cells, they still carry the potential for significant addiction and dependence. Regular use can lead to a need for the drug to relax, with dependency developing after just a couple of weeks.
Withdrawal from benzodiazepines can be prolonged, with painful symptoms persisting for months or even years. Rapid cessation poses severe risks, including seizures and even death.
The Development of Xanax and Other Benzodiazepines
As research progressed, chemists created a variety of benzodiazepines, including Xanax, approved in 1981 for anxiety and panic attacks.
Xanax is a fast-acting medication, providing quick relief but also leading to rapid dependency due to the brain's reward response to quick-acting drugs. Klonopin, in contrast, acts more slowly and may be less psychologically addictive, though it still carries significant risks.
Each benzodiazepine has unique characteristics, but withdrawal from any of them can be severe and debilitating. The intensity of withdrawal symptoms typically runs counter to the effects of the drugs themselves.
The Arrival of Z-Drugs: Ambien and Lunesta
As benzodiazepines fell out of favor, pharmaceutical companies pivoted to developing new "safe" sedatives, such as Ambien and Lunesta, often marketed with appealing imagery.
Despite being labeled as "non-benzodiazepines," Z-drugs share similar mechanisms of action, enhancing GABA's effects in the brain. This leads to comparable risks of addiction and withdrawal, which are often misrecognized by medical professionals.
I initially became dependent on Ambien, which provided effective relief from insomnia but ultimately caused me to rely on it more heavily over time. I later transitioned to Lunesta, which was prescribed as a safer alternative, but withdrawal from it was severe enough to land me in the emergency room.
The Challenge of True Safety in Sedatives
The central issue in the search for safe alternatives to sedatives lies in the brain's adaptability to substances. Withdrawal symptoms frequently oppose the drugs' effects, leading to worsened conditions. This cycle perpetuates the necessity for increased dosages, often culminating in dependency.
The non-benzodiazepine anticonvulsants discussed in the Quillette article function similarly to benzodiazepines, either boosting GABA or reducing glutamate. While they may be less psychologically addictive, the potential for dependence remains.
Understanding Addiction and Dependence
In the case of opiates, safer alternatives like methadone exist, helping to manage cravings while still leading to withdrawal symptoms. Similarly, while benzodiazepines present a lower overdose risk than barbiturates, their potential for addiction and withdrawal symptoms is severe.
Addiction typically refers to the psychological draw towards a substance, often linked to dopamine spikes in the brain. Dependence, however, relates to the physical need for a substance, leading to withdrawal symptoms upon cessation.
Ongoing Research for Ideal Anti-Anxiety Drugs
Scientists continue their quest for an ideal anti-anxiety medication that could minimize harmful effects while maximizing benefits. Preliminary findings indicate that different GABA receptor subunits can produce various effects, and researchers are hopeful about isolating these desirable effects.
However, even if a non-addictive medication is discovered, the risk of tolerance and dependence may remain, as the brain continually seeks homeostasis.
Evaluating the Safety of Medications
Our societal focus often centers on addiction, overlooking the reality of dependence, which can affect anyone. A significant percentage of the population is likely dependent on sedatives or antidepressants, with many facing withdrawal symptoms when unable to obtain their medications.
Despite the potential benefits of transitioning from alcohol to "safer" drugs, the long-term effects of many medications remain uncertain. The perception of medications as harmless often leads to increased daily use, coupled with a lack of awareness regarding the associated risks.
In conclusion, the search for truly safe sedatives is fraught with challenges. Until a solution is found, the cycle of addiction and dependence may persist, leaving many to grapple with their struggles.