Psychopharmacology studies the effects of all drugs and stimulants on behavior through the brain and the rest of the central nervous system.

What is the definition of psychotropic drugs?

Psychopharmaceuticals are all substances that affect behavior via the brain and the rest of the central nervous system. Substances can influence behaviour, because behavior originates from signals in the brain and these signals can be influenced by chemical reactions with substances from the outside. The brain transmits signals to the spinal cord, and the spinal cord in turn transmits signals to muscles and organs. The pattern of muscle activity, or behavior, is therefore ultimately determined by reactions in the brain.

A distinction can be made between two categories of psychotropic drugs: stimulants and medicines. Stimulants are psychotropic drugs that people take for their rewarding effect. This rewarding effect can be addictive: the drug is administered repeatedly to achieve the rewarding effect. Drugs are psychotropic drugs that are used to influence problematic behavior. Problematic behavior means that, according to the person himself or others, there is dysfunction.

Signals between nerve cells are transmitted through neurotransmitters. There are also other substances that provide signal transmission in the body. Hormones are specific substances that transmit messages through the bloodstream. This mode of signal transmission is slower (a few seconds) than that of neurotransmitters (a few milliseconds). Hormones can also be used as psychotropic drugs.

How can psychotropic drugs be taken?

Psychiatric drugs can be taken in different ways:

• First, psychotropic drugs are ingested through food. These are proteins that are broken down into amino acids. Amino acids are converted in the brain into neurotransmitters, which play an essential role in signaling in the brain. An example is the amino acid tryptophan, which is necessary for the production of serotonin.
• Secondly, psychotropic drugs can be administered by means of a pill. When administered via a pill, the psychopharmaceutical enters the brain slowly: it goes through the stomach via a detour, so that the maximum concentration in the blood is reached after a few hours. As a result, a large part of the psychotropic drug is broken down along the way. This also applies to intake through food. Exactly how long it takes for a psychopharmaceutical to enter the blood differs per substance.
• Other ways to take psychotropic drugs are through the skin (such as nicotine patches), through the mouth (such as nicotine gum), through the nose (such as nasal spray or cocaine sniffing), smoking and injecting. The order is equal to the speed at which the substance is absorbed into the blood: through the skin is the slowest way, injecting the fastest way.

When taking via a pill, two types of packaging are possible. These lead to differences in the way the psychopharmaceutical is absorbed in the blood. The first way leads to the fastest possible absorption into the blood, but the value also drops quickly. To reach the peak value again, the drug must be taken again. The second way ensures that the psychopharmaceutical is absorbed less quickly into the blood, but this keeps the concentration in the blood more constant and the effect lasts longer. This is called extended release.

How is the dosage of psychotropic drugs determined?

How much of a certain substance must be taken to achieve the desired effect depends on the substance. For example, caffeine already has an effect at 1 microgram per milliliter of blood, while alcohol has an effect at 0.5 milligram per milliliter of blood, so 500 times as much alcohol is needed to achieve a noticeable effect. The relationship between dose and effect can be represented in a dose-response curve (see chapter 5).

With the dosage, it is important to take into account the ease with which someone takes more of the substance. An extra glass of beer or cup of coffee is soon consumed. However, a pill allows more control over the dosage. This also allows more control over the occurrence of side effects.

In addition to the desired effects, most psychotropic drugs also have undesirable effects: so-called side effects. The balance between the desired and undesired effects at a certain dosage is of great importance. A therapeutic window indicates the lowest dose to achieve a desired effect and the highest dose to avoid too many side effects. There are individual differences in the optimal dosage. Therefore, a substance with a wide therapeutic window is better suited for the treatment of a symptom or syndrome.

Setting the optimal dosage of a substance is called titration. This is easy with substances that have an immediate effect. However, most drugs have to be administered over a long period of time before the effect occurs, making the first dose an experiment that takes several weeks. If the balance between desired and undesired effects is not optimal, a new test period must be started with a different dose.

During a lengthy titration process it is problematic if tolerance develops. This means that the effect of the substance decreases due to chronic administration.

How is psychopharmacological research usually done?

A distinction can be made between explanatory and predictive research. Explanatory research means looking for the mechanisms behind the action of psychotropic drugs. Predictive research means that it is investigated whether the psychotropic drugs are effective.

In psychopharmacological research, the emphasis is usually on predictive research, looking at whether drugs have the desired effect. However, this is the last phase of a research trajectory, which is preceded by the preclinical phase in which explanatory research is done. An explanation for the effect of a medicine can form a starting point for interventions.

Which criteria are important in psychopharmacological research?

In order to conduct psychopharmacological research properly, the following criteria are important:

• Placebo control: using a control group that receives a placebo without the active psychotropic drug.
• Double-blind study: patients and researcher do not know who is in the control group and who is in the experimental group. This prevents differences in outcome based on expectations.
• Conclusion: if there is a systematic effect in the experimental group, which is greater than in the control group, it is concluded that the effect is due to the drug. If there is a systematic effect compared to doing nothing, both in the control group and the experimental group, it is concluded that the effect cannot be attributed to the drug, there is a placebo effect.
• Sample: The sample should be as balanced as possible. If this is not the case, then differences between groups in the effect can be attributed to, for example, differences in age or level of education. Balancing the groups can best be achieved by random composition.
• Baseline measurement: there can always be confounding factors, despite random assignment to conditions. To gain insight into this, a baseline measurement is performed. This makes it possible to check whether there are differences between the groups on the variables that are measured prior to the study.

After the research, it is decided whether the drug can be marketed. The most important criteria are whether the desired effect occurs and whether there are too many/too serious side effects. Despite careful consideration, sometimes problems arise when a drug is used. These observations should be statistically analyzed to investigate whether the problems can be associated with substance use. The odds ratio is used for this: the chance that the side effect will occur when the medicine is used. In addition, the seriousness of the problems is important. In the case of statistically negligible but very serious problems, such as the occurrence of suicidality, it may be decided to withdraw the drug from the market.

What is Preclinical Research?

Preclinical research mainly uses laboratory animals. Mostly these are rodents, because the chemical reactions in the brain are very similar to those in humans. However, the organization of the brain is different, so results are not fully generalizable to humans. That is why preclinical research is also done among patients, in which it is examined exactly what happens in the human brain.

In clinical research (predictive research) there are generally three phases:

1. Determining appropriate doses, through a titration process in a small group of healthy volunteers.
2. Investigating the therapeutic effect in a small group of patients. This is done double-blind and placebo-controlled.
3. Large-scale double-blind and placebo-controlled patient research, preferably in several countries, at least two independent studies. These are the phase 3 clinical trials and last an average of 3 ½ years.

If the results are positive on the basis of phase 3, the drug is registered and the phase 4 study begins. During this phase, pharmacists and prescribers keep track of the side effects that still occur among users as accurately as possible.