More Drugs (Part 3)
Mood Stabilizers and Newer classes of drugs
The class of drugs labeled, “Mood Stabilizers” raises interesting if not elusive questions about who we are and how we feel.
What is Mood?
The word, “Mood” is defined as: (noun) A temporary state of mind or feeling. For example: "He appeared to be in a very good mood about something." Defined as an (adjective): Inducing or suggestive of a particular feeling or state of mind. Example: “Mood Music.”
What is Mood? First, Mood is a temporary versus a permanent state of feeling. When a person says, “Dr. I feel sad.” This is the expression of a specific emotion. Sadness. The definition of Sad, which I have discussed in other entries, is a qualitative internal experience and it brings from memory a certain kind of emotion. The feeling of sadness is clearly different than the feeling of happiness. Mood, on the other hand, is not a particular feeling, rather it is a state of feeling. By “state” I mean an environment or an ambience so-to-speak that promotes a certain kind of emotion. When you feel sad it is usually a manifestation of an emotion within a certain type of mood state. You usually don’t feel sad when you are in a positive mood state, for example.
Second, One’s mood is considered normal when it is stable (not shifting). Shifting mood, for whatever the reason, is more difficult to deal with than stable mood. “One minute this person feels in a positive frame of mind and the next minute this person is in a negative state of mind. What kind of a mood state is this person really in? The best answer might be a “fluctuating” mood state. In this case, it would be hard to trust the mood this person is in.” If you are characterologically stable in your mood, you might be given a label, “That guy over there is a curmudgeon (a bad-tempered or moody person). A curmudgeon is a person whose mood is almost always poor (or low). Everything a curmudgeon says is a “downer” because the curmudgeon is in a perennially poor mood state. Even though it is low or negative, it might still be easier to deal with this person than with a person whose mood is shifting or fluctuating. A curmudgeon is predictable, this person is always in a bad mood. Mood state gone awry mostly in the positive or grandiose direction is often diagnosed as “mania.” If a person’s mood state is perennially low or bad, we don’t really have a name for it. We simply call it, intractable depression.
Mania defined is: (noun) mental illness marked by periods of great excitement or euphoria, delusions, and overactivity.
Here, I presume, mania is juxtaposed to depression. Very high versus very low and the fluctuations between very high and very low mood is a characteristic of a manic state with mania defined as the very high end of the continuum. From a clinical perspective, both very high or very low mood is troubling, even problematic. Drugs might be employed to treat a fluctuating mood state. One type of drug is a “mood stabilizer.”
What are mood stabilizers?
People have all kinds of home-grown psychological strategies they employ to stabilize their mood. Meditation is a popular method. In society, the more stable (or even) your mood, the easier you are to deal with, and by deduction, it is assumed that you feel better about yourself. This underscores the term, reactive (or its opposite, non-reactive or stable). Reactive is a label when it comes to mood disorder that reflects fluctuation in a brief time interval between very high and very low. No one likes being around a reactive individual. I would presume when a person is in a reactive state that person, as well, doesn’t feel content or at peace or settled with him or herself either.
Bipolar Disorder tends to be lumped into the description of people whose mood stability has gotten out of whack. In literature, think about the Robert Louis Stevenson story of Dr. Jekyll and Mr. Hyde. Interestingly, a closer look at this story reveals that Dr. Jekyll had a drug-induced mood disorder. As the story goes, Jekyll had discovered some powders (that he got somewhere in East India) that when he ingested them, they started shaping his whole personality. The manifestation of this character alteration were wild shifts in Dr. Jekyll’s mood, especially when he poorly measured the amount of powder he took at any given time. This drug-induced mood shifting, as it got more out of control, started scaring Dr. Jekyll himself, so in addition to shifting mood, Dr. Jekyll began experiencing breakthrough bouts of anxiety which amplified his mood shifts. The powder also made him really sick, so Dr. Jekyll knew if he kept taking it, the powder would eventually kill him. But, take it he did, and the consequence of this action produced the tension in the Dr Jekyll and Mr. Hyde story. It ultimately ended in his demise.
From this story, it seems we all want stable mood. We avoid situations or circumstances that cause our mood to shift too much beyond what we consider normal. But, when mood starts shifting wildly because of some internal forces (like from a drug, or from brain metabolism gone awry) we begin to worry.
What’s wrong with me?
This is where mood stabilizers come in.
What is Lithium?
Lithium is perhaps the first modern mood stabilizer. It is the lightest of all metals in the periodic table of elements, with a density only half that of water. Lithium (also known as a Mineral Mood Stabilizer) is more than a metal, it has the properties of a mineral that reacts to organic chemical structures. When Lithium is taken into the body and then crosses the blood-brain barrier, it reliably induces several specific biochemical and molecular effects on brain operation. First, at a molecular level, this mineral acts on neurotransmitter/receptor-mediated signaling in brain chemistry. This occurs in several ways: 1) signal transduction cascades, 2) hormonal and circadian up-regulation, 3) ion transport, and gene expression facilitation. I won’t go into further detail here, but suffice it to say that the action of Lithium is activation of neurotrophic pathways (neurotransmitter communication) underlying the the pathophysiology of Mania.
Regardless of the super complex process by which Lithium interacts directly with brain chemistry, in some people under some circumstances, at enough of a dose, Lithium does seem to work and individual mood stabilizes.
What are Mood Stabilizers like Lithium? How do they work?
Mood Stabilizer drugs, like Lithium, have a long history of use for mental illness, mostly for intractable depression, or more recently bipolar disorder. Lithium was given to patients with mania in the late 1800s. Physicians in Denmark are credited as the first group of professionals who delivered these drugs to patients, likely intravenously. It was an Australian psychiatrist John Cade who, in 1949, published an initial scientific paper on his use of lithium (he labelled it, a salt) to treat acute mania. Why and How did Lithium work? Who knows, especially in 1949. Again, it was the TRIAL and ERROR approach that was employed in this early treatment research. If it works, why not keep using it? Right?
Since then, Lithium has become the most widely used mood stabilizing drug in existence, world-wide. Although, the clinical effects of lithium were not understood especially in the early years of its use, it was possible to replicate the chemical properties of this naturally occurring salt (or mineral), and so other copycat mood stabilizers were synthesized: carbamazepine, valproic acid, for example. These synthetic mineral compounds were used, along with Lithium, in the 1970s and 1980s in the United States to address mania.
Modern View: How does Lithium Work? In brief, it seems Lithium (and Lithium-type drugs) exert a neuroprotective effect (they prevent brain matter damage and degradation) and neuroproliferative effect (facilitate neurotransmitter communication). These two effects are supported by MRI evidence of preservation of brain grey matter. This is when MRI’s are given multiple times to one patient and the amount of grey matter does not show deterioration with time. At a deeper level, the exact mechanism of these effects, remains elusive, but the clinical implications are fairly clear; that is, the effects seem to repeat in patient after patient on these drugs.
Lithium Side Effects
Unfortunately, introducing a metal (or mineral or salt) into the brain produces a whole range of tough side effects. It is, for example, very hard on the kidneys to metabilize the by-products of Lithium. The kidneys must ultimately must flush out this metal because after the lithium has acted on the brain it becomes toxic to the body and all of the organs in the body. It is a hard metal to filter out, so the kidneys must work overtime to do so. The more Lithium in the body, the harder the kidneys must work and the less effective they become. Most of the side effects I’ve listed below are the result of kidney damage as a consequence of discarding Lithium waste from the body.
Nausea
Fatigue
Tremor
Weight gain
Confusion
Diarrhea
Other Drugs Besides Lithium
The other drugs that have been used to treat mood shifting besides Lithium (and Lithium Copycat Drugs), are the antipsychotic drugs and anticonvulsant drugs (which were originally designed to treat seizures and epilepsy).
Antipsychotic Drugs for Mood Disorder:
I’ve listed below some of the more common antipsychotic drugs in use today to treat abnormal mood shifting.
aripiprazole (Abilify)
olanzapine (Zyprexa)
risperidone (Risperdal)
lurasidone (Latuda)
quetiapine (Seroquel)
ziprasidone (Geodon)
asenapine (Saphris)
The story of antipsychotics and Mood Disorder is a mixed story. Why would these drugs work with mood disorders? What are the risks of taking anti-psychotics if your issue is not psychosis, but mood instability per se? Plus, when you take these drugs, you body gets used to these drugs and they are not easy to quit, so the costs of these drugs, especially if you stay on them for a long time, is that you are putting yourself in a life-long experience of taking drugs just to maintain reasonable or normal mental health and that mental instability (or at least the cause of it) is blurred between drug effects and mental dysfunction. This is a vicious cycle.
As noted in previous entries in this blog, there are some substantial side effects related to brain-levels of dopamine which this type of drug depletes that cause troubling life-long side effects related to fine motor control and physical movement. Some of these side effects, like tardive dyskinesia, are not reversible even if you stop taking the drug. More contemporary drugs have less risk for these side effects, but the risk is still there, particularly if your brain is vulnerable to low-dopamine states.
Anti-Convulsant Drugs for Mood Disorder:
Carbamazepine (Carbatrol, Tegretol, Epitol, Equetro)
Oxcarbazepine (Oxtellar, Trileptal)
Gabapentin (Horizant, Neurontin)
Topiramate (Qudexy, Topamax, Trokendi)
Anticonvulsants work by calming a hyperactive brain. In some ways they are the same as CNS depressants such as Xanax and even alcohol, but their mechanism of action is much different than CNS depressant drugs. Therefore, the side effects are different, some might say, less severe or problematic. This calming of hyperactive synapse transmission in the brain is the primary reason some of these drugs are used to treat epilepsy, prevent migraines, and treat other brain disorders including rapid cycling (4 or more mania cycles per year), or mood instability.
Each of these drugs has a slightly different effect and the interaction of this effect with the unique physiology of a given person, or so the story goes, is why different specific drugs are used for different persons with different disorders. For example: Depakote and Tegretol tend to be more effective in treating mania than depressive symptoms while Lamictal appears to have stronger antidepressant effect.
The history of anticonvulsants for treating mood disorder goes back to the TRIAL AND ERROR method. Practitioners and researchers in a frantic attempt to identify drugs that to treat mood disorders (bipolar disorder) stumble across these drugs as having an impact on mood. They start trying them out on people with mood disorder and discover that these drugs work better than giving the patient nothing or simply giving a placebo drug. After a whole bunch of trials with this drug where the effects seem to hold up, the drug then gets approved for use with this group of persons; persons with mood disorders.
At first, anticonvulsants were prescribed only for people who did not respond to lithium or antipsychotics. Today, they are often prescribed alone, with lithium, or with an antipsychotic drug to control mania. Even in this regard Valproate is the only anticonvulsant thus far approved by the FDA for the specific treatment of mania specifically. This is perhaps the newest line of approved drug treatment for mood disorder.
Anticonvulsant side effects
Anticonvulsant drugs have a long list of side effects. This makes sense because the drug is impacting the entire brain, not just small components of brain physiology or neurotransmitter communication (like Lithium). So, these drugs are associated with a role range of side effects: fever, dizziness, drowsiness, blurred vision, nausea, vomiting or mild cramps, headache and skin rash, not too different than is experienced with CNS depressant drugs. A good feature about the drugs (that may not be the case with antipsychotics) is that the side effects reverse when the drug is withdrawn. This means there is less danger in prescribing these drugs to treat mood disorder.
Whether it is worth taking these drugs with their side effects is a judgement call on the part of the person suffering from the mood disorder. But, generally, the approach has been to try the drug, experience the side effects, if the side effects are tolerable, stay with the drug, and hope that the main effect of the drug is mood stabilization.