Other Drugs - Part 2
Drugs for conditions other than depression
Anti-Anxiety Agents
Anti-anxiety agents are drugs designed to treat anxiety.
Anxiety is not depression. Anxiety does not look or feel like depression. Some people think that anxiety is the opposite of depression. But, this is incorrect. The relationship between anxiety and depression is much more complicated.
What is Anxiety?
I took this up in a previous blogpost. I review it here again, from the perspective of psychopharmacology. At a fundamental level Anxiety = Fear.
In fear, there is an object. The famous anxiety analogy, sometimes attributed incorrectly to Freud (it was really William James who is the author of this idea): If a “bear is chasing you,” you feel fear. In anxiety, “you feel fear, but no bear is chasing you.”
Anxiety is fear without an object (fear with no bear). You might thinking about a bear and then you start to feel fear. This is also a kind of anxiety, especially if you think you might encounter a bear, “anticipatory fear.” Anticipatory fear = worry, but I will take this up in a later entry on the topic of “Worry.”
In a story about a bear, you might feel fear, although there is no chance you will ever experience a bear, this is “fantasized anxiety.” People feel fantasized anxiety every time they watch a horror movie and get a danger sensation though they are only sitting in a movie theatre.
Anxiety boils up from within the brain, but it is often stimulated by something external. Then it turns into a psychological and physiological fear response as the figure below shows the brain’s response to a spider phobia.
Note the (blue) “higher order circuit" because it is essential that the spider is interpreted by the brain as a threatening object. I like this figure because it’s simple and straight-forward. Anxiety mobilizes you for action (avoidance).
In this figure, forecasted and conditioned action are not the same. Forecasted action stems from fantasized or anticipatory fear; conditioned action comes primarily from a primal survival circuit. In conditioned action, you don’t know why when you see a mouse, you jump and run, but this fear is so deeply ingrained (or conditioned) that you do it before thinking about it. In either case threat avoidance is the primary goal.
Fear, then, is the phenomenology (or personal experience) of the human threat-avoidance mechanism. Anxiety is never pleasant, but it can be empowering - empowering when you run under the condition of fear. Although, if there is no object, you are not sure what you are running from. You do feel that you are getting away, and at one level, this escape feeling is exhilarating. Your heart is pumping, your breathing is deep and heavy, you are running, soon, you will be safe. This is the end-state of anxiety when you are released (or freed).
In the medical world, there are seven recognized anxiety syndromes:
1. panic disorder, 2. agoraphobia, 3. social anxiety disorder (SAD), 4. generalized anxiety disorder (GAD), 5. specific phobias (spider phobia as in the figure above), 6. obsessive compulsive disorder (OCD) and 7. post-traumatic stress disorder (PTSD)
The story of anti-anxiety agents is not a story of success. In fact, over the past 50 years researchers and scientists have essentially failed to produce any drugs that effectively treat anxiety disorders. Sure, there are a lot of drugs for anxiety, including but not limited to anti-depressant drugs (or SRI or SRNI inhibitors), anti-psychotic medication impacting the GABA system, and natural drug treatments like cannabis or alcohol, but nothing really “treats” anxiety. At best, these drugs treat only the symptoms of anxiety particularly the upregulating processes that get a person ready to run away. Take alcohol, which is a central nervous system (CNS) depressant. All alcohol does is shut down or dysregulate the CNS. All Xanax (or alprazolam) does is shut (or slow) down the CNS. Nothing more. It does not treat the subjective experience of anxiety, it just masks it for a while until the drug wears off.
The best that science has come up with has been drugs that mask the symptoms of internal anxiety by creating a profound, but short-lived sense of, euphoria as in the Figure above, is the case when the effects of a benzodiazepine (Xanax) acts chemically on the brain to produce a calming effect by increasing the brain’s production of the the natural chemical in the body known as GABA (gamma-aminobutyric acid).
So, How does one treat anxiety?
The answer to this is also fairly straight-forward. It is through helping the client re-interpret the stimulus (as in the spider in the figure above) as no longer threatening. So, when a person encounters a spider, the person no longer feels fear of threat in the presence of the spider. This is altering a personal subjective appraisal state, it has very little to do with drug effects (it is, rather, the mind mediating reality). And, in fact, drugs are nearly worthless in helping a client re-interpret the meaning of the world.
This being said, there are still a large number of drugs that can effectively mask a psychic fear response:
Listing of Anti-Anxiety Drugs
alprazolam (Xanax)
chlordiazepoxide (Librium)
clonazepam (Klonopin)
diazepam (Valium)
lorazepam (Ativan)
These drugs all fall under the heading of benzodiazepines. Think, phenobarbitol - one of the first benzodiazepines with awful and lethal side effects, Newer drugs are safer with less side effects in the short-term, but they are all still addictive. Most people will, over time and regular usage of anti-anxiety drugs, develop a physical dependence on them. Typical side effects (some desirable and some not) include dizziness, euphoria, light-headedness, slurred speech, and memory problems.
Since benzodiazepines only mask the effects of anxiety, it is important to know precisely how long they will work. The strategy for timing when a drug loses its effectiveness is the drug’s half-life.
What is half-life?
Half-life is the time it takes for the amount of a drug's active substance in your body to reduce by half. This depends on how the body processes, metabolizes, or otherwise gets rid of the drug. Half Life can vary from a few hours to a few days, or sometimes weeks.
Anti-anxiety agents have their place in psychopharmacology and other types of therapeutic treatment for anxiety. For one, these drugs act quickly. They are also precise in their masking effects, and short-lived. The side effects are relatively small in comparison to other drugs like antipsychotics. So, they are often employed along with psychotherapy for reframing the fundamental nature of anxiety itself.
Stimulants
As our world becomes more complex, the demands on our attention, vigilance, and strategic focus as well as dual tasking will increase, and markedly. Over the years, people have started to notice the those persons who vary in their capability to sustain attention to a single or a very few essential tasks. Obviously, this issue is prominent in the public schools where children are pushed to stay on task to negotiate school assignments with very little teacher oversight or even instruction. When children are off task, they have nothing to keep their minds attentive, so they get into trouble. This behavioral problem has spawned (starting in the 1930’s) the belief that some children who are unable to focus their attention to a very high degree on school-related tasks (boring or not) as having some kind of structural brain or neurological damage. This is when the label ADHD emerged (Attention Deficit Hyperactive Disorder).
I don’t want to linger too long on this issue, because as a society we don’t know how to change our social structure to meet the rapidly diversifying needs of children, so we decide, as a society, to change the children instead of altering their learning environment (just like when society couldn’t tolerate anyone who used their left hand to write with, instead of making left-handed desks, they decided to force left-handed children to write with their right hand - tying the left hand behind the child’s back and so forth). This produced a whole class of children with the disorder, “forced-dextrosity.” Forced dextrosity is linked to dyslexia, stuttering, and other speech disorders. One problem address others created. ADHD is a similar issue, only it is not handedness, it is attentional focus.
Although there are a rare minority of cases where attentional deficit is truly an attentional deficit in a given child, a great number of children are simply not behaving to unrealistic social standards, so the easiest way to address this is to medicate the child in a way that pharmacologically focuses their attention and pharmacologically straps them to their seat at school (or at home).
A class of drugs evolved to address this problem. These drugs are commonly known as Stimulants, designed to upregulate attentional processes and increase levels of vigilance and focus in a given individual.
What could be wrong with this? Right!
Increasing attention and vigilance and focus is what every person wants. But, it doesn’t work for everything. For one, it can diminish creativity. Two, the side effects of these drugs engage an almost opposite rebound response, so that as the child becomes more dependent on these drugs, if the child goes off the drug, then even worse ADHD symptoms ensue. So, from a parental point of view, this becomes a vicious defeating circle.
Stimulants are a lot like anti-anxiety agents because they really don’t address the the issue (mismatch between learning methods and individual child differences). They simply upregulate the child’s brain (at a long-term cost to the functioning nervous system of a given individual) and the drug over-regulates, temporarily, the Central Nervous System to get the desired behavior from the child (or adult). The listing of stimulants are highlighted below.
A new term has emerged in the literature of adult mental health. This is Adult ADHD (or chronic inattention in adulthood, from 18 years and older through the adult lifespan.). The problem here is also obvious, the story so predictable, that you would think someone would have figured out a long time ago that society is heading down a rathole of sorts by pharmacologically damaging children (and now adults) with drugs to get a desired short-term behavior, but that may not be useful for long-term adult productivity and adaptivity and health. But, it seems to get the desired result in the short run, Why not? This is how the thinking goes.
Aptensio XR
Metadate ER
Concerta
Daytrana.
Ritalin
Ritalin LA
Methylin
QuilliChew.
The most commonly prescribed adult stimulants are:
Adderall (amphetamine/dextroamphetamine)
Ritalin and Concerta (methylphenidate)
Dexedrine (dextroamphetamine)
Vyvanse (lisdexamfetamine)
There really is no difference, pharmacologically, between the childhood ADHD stimulants and the adult stimulants. the only difference is the amount prescribed. Like anti-anxiety agents, these drugs mask the problem for a while and they certainly do not deal with the long-term implications of inattention.
Antipsychotics
Antipsychotic drugs have probably the longest history of the drugs that modern medicine has prescribed for a mental health condition. In fact, psychiatry, as a medical specialty, is built principally on the back on antipsychotic drugs.
What is Psychosis?
Psychosis is not a diagnosis. Schizophrenia is a diagnosis, you can look up schizophrenia in a book and it has a taxonomy. Psychosis does not. Psychosis is simply an agreed-upon term that describes a kind of phenomenology experienced in a comprehensive brain-behavior breakdown. Psychosis is a break with what people view as reality (whatever that state of being is). In Psychosis, the break from reality occurs when thoughts and perceptions are so disrupted that the person is unable to communicate with anyone else. These changes generally happen gradually, typically in three phases: 1. early, 2. acute, and 3. recovery. Psychosis is not permanent, but likely recurring. This is why it is thought to be a structural breakdown of brain structure or process (like Alzheimer’s Disease only psychosis is not progressive, permanent and it is treatable) and it doesn’t happen due to just old age.
What are antipsychotic drugs?
The first antipsychotic drug introduced to the public was Chlorpromazine followed by a large number of other antipsychotic derivative drugs, many with diverse chemical structures. So far, no antipsychotic drug has been shown to be more effective than chlorpromazine in treating schizophrenia. This is probably because the mechanism of antipsychotic drugs has not changed since the earliest modern drugs: Chlorpromazine, Thorazine and Stelazine were introduced in the in the 1950’s. Essentially these drugs block the neurotransmitter dopamine. This was found in clinical trials to dramatically reduce (and sometimes eliminate) psychotic symptoms for many people diagnosed with psychotic-like disorders such as schizophrenia. The Royal College of Psychiatrists report that nothing works as well as antipsychotic medications to treat schizophrenia. Whether this is true or not is debatable, but antipsychotic drugs are certainly the mainline way of thinking about schizophrenia in our modern age.
Unfortunately, there are some big issues if dopamine is totally blocked. The neurotransmitter dopamine is a fundamental building block of coordinated human movement. Certain structures in the brain including the substantia nigra pars compacta (SNc) in the midbrain with the dorsal striatum (i.e., the caudate nucleus and putamen) in the forebrain are connected by this nigrostraital pathway.
This pathway is filled with dopaminergic neurons that communicated with each other via dopaminergic neurotransmitters. I apologize for all this brain terminology, but it is the only way to make the point that when dopamine is blocked, this pathway is damaged and over time this damage to this pathway becomes permanent. This is why these drugs cause a severe side effect called tardive dyskenisia (TD). What happens when this mechanism is damaged is that it becomes difficult for an individual to engage fine motor control, so you start to see manifestations of this damage in symptoms similar to parkinson’s disease or other neurological symptoms like the propensity to stick-out-ones-tongue in a rapid movement. These are not only annoying symptoms, but they can substantially impact quality of life. With some of these earlier drugs like thorazine and stelazine, this pattern of behavior becomes permanent with long-term usage.
Listing of Antipsychotic drugs
aripiprazole (Abilify)
asenapine (Saphris)
cariprazine (Vraylar)
clozapine (Clozaril)
lurasidone (Latuda)
olanzapine (Zyprexa)
quetiapine (Seroquel)
risperidone (Risperdal)
Antipsychotic drugs are also used with patients with depressive symptoms and or other concerns such as OCD. For example aripiprazole (Abilify) has been approved by the FDA (Food and Drug Administration) in small doses for depression and for OCD symptoms. Why would these drugs be good for depression and/or anxiety and/or OCD symptoms? The answer is: TRIAL AND ERROR. Researchers and practitioners have tried these drugs with people who have all kinds of psychiatric disorders and have discovered that sometimes these patients report feeling better, so working backwards, they deduced that dopamine is connected to brain mechanisms underlying depressive and obsessive symptoms. Perhaps anything would reduce depression in any given group of people, but when there is a repeated beneficial effect, the drug then gets treatment approved by the FDA.