Chapter 1
Psychotropic drugs can have an influence on the brain and the muscles, what we call
behavior. Drugs can be recreational and medicinal. Some drugs have a very strong reward
effect, which can suppress hunger and sleep. These drugs are more likely to lead to
repeated self-administration, also called addiction. Psychotropic medication is used to
reduce, change of control problematic behavior.
1.1: Intake
Amino acids from eating food can be converted into neurotransmitters, so it's also a kind of
drug. But medicinal drugs are most commonly taken via pills. However, this is not a very fast
and effective way since it has to pass the stomach and other organs before it can enter the
bloodstream. Injecting a substance or smoking has the fastest effect. There are two ways to
‘package’ a medication in a tablet:
1. The fastest possible increase in blood levels, up to a maximum value. Then the drug
will be in the blood in one hour and will decrease by half in around 4 hours. After this
a combination can be used with the second packaging method.
2. The second packaging method: releases the medication into the bloodstream more
slowly, to achieve a more constant blood level for around 8 hours. It's also called an
extended release formula. Advantages are that the effects on behavior are more
gradual and that the drug only needs to be administered at the start of the day.
Another type of substance is one that is composed of hormones. These take longer to be
transported in the bloodstream, because they need to go to another part of the body.
1.2: Dosing
The effects do differ per substance. Caffeine has a desired effect at 0.5 mg/kg, and does not
increase in effect with a higher dosage. Alcohol will produce an effect at 5-10 grams. A small
dosage of alcohol has a bigger effect than a small dosage of caffeïne. Therefore pills are an
easy way to administer, because you can choose the dosage in a tablet to limit side effects.
1.3: Side effects
Alcohol can be in some circumstances more pleasant than in other circumstances, and the
amount of alcohol can also vary in pleasantness. The therapeutic window is determined
on the one hand by the lowest dose that forms an average lower limit for observing any
desirable effect, and the upper limit that is the highest average dose that results in an
unacceptable level of undesirable side effects. The larger this window, the more suitable
the substance is for treating a symptom of syndrome.
1.4: Titration and tolerance
With titration you can determine the optimal dose. For most psychoactive drugs the desired
effect is only achieved after chronic administration, usually for a period of two to six weeks. In
20-40% no dose of the drug can be found to achieve an acceptable result.
One possible result of the titration process is the possible development of tolerance:
reduced desirable or undesirable effects due to chronic administration of a substance. You
can compensate by increasing the dose, but that has disadvantages as well. This happens
in certain types of addiction.
, 1.5: Research into how psychotropic drugs work
The goal of psychopharmacological research is to determine whether the drug has the
desired effect in a specific group of patiënts, without explaining why it has that effect. It’s
more a prediction. But before we research this there is a pre-clinical phase, in which
explanatory research is necessary. When a drug has a lot of side-effects, the phenomenon
behind the drug can help us create a better one without the undesirable effects. But this
rational drug development is rarely the case, normally we find drugs accidentally, when the
substance was initially intended for other purposes.
1.6: Placebo control
An open label study is when the drug is administered to a group of patients in full view of
everyone involved, and then the researchers can conclude that it may indeed be due to the
substance. If this is the case, then it will be followed by a placebo control study. If both
groups score the same on tasks, it can be because the drug is not useful or there is a true
placebo effect: the patients in both groups expect to be administered with an active
ingredient, and both experience effects.
1.7: Random tests and statistics
Research in the effectiveness of the drug involves a double-blind (the patiënt and the
researcher does not know who took what, it will reduce the influence of expectations)
comparison between two groups, one of them receives the drug and the other receives a
placebo. It is important to take a balanced random sample, and that they are representative
of the total population. Baseline measurements make it possible to determine whether
there are clinical differences between the groups and to correct the eventual clinical results
for any a priori differences between the groups. The scores are expressed after treatment as
a (percentage) change from the baseline value. If there is a sufficient improvement, the drug
can be released to the market. However, one has to take into account the side effects. There
needs to be a statistical consideration: the side effect needs to be quantified and analysed in
terms of probability. Also the seriousness of the side effects need to be taken seriously.
Inset 1.2: calculate the odds ratio. With the odds ratio you can check the
likeliness of side effects, and if there is a relation between the drugs and a
side effect.
1.8: Pre-clinical and clinical research There are three (till four) phases:
1. A small group of healthy volunteers is used to study which doses
can be tolerated without problems, by the titration process. Heart rate, blood
pressure, respiration and muscle spasms as well as subjective experiences are
monitored.
2. Study therapeutic effects in a small group of patients. It is a double-blind placebo
study. This can also be with similar existing drugs as an extra condition to check if the
new drug is better.
3. Study therapeutic effects in a large group, as well double-blind placebo. This takes
around 3.5 years and is very expensive. This will be done by impartial researchers,
and the industry will fund them. The responsibility for ensuring the quality of the
research will be in the hands of organisations that would eventually evaluate whether
the drug can be admitted for regular use.
4. Recording side effects that may occur as accurately as possible.
