What To Know About Antidepressants

Antidepressants, also known as thymoleptics, are a class of chemically different drugs that are used to treat depressive disorders, anxiety disorders, obsessive-compulsive disorder and chronic pain and have very different efficacy profiles. Their effect is based on a brightening of the mood and an increase in drive, which is also accompanied by a reduction in the physical symptoms of depression. In principle, there is no potential for dependence.

The first antidepressant was imipramine, which was discovered in 1957 by the Swiss psychiatrist R. Kuhn. Previously, depressive patients were treated with opium or somnifen and barbiturates to induce prolonged sleep. Since the discovery of imipramine, numerous other tricyclic, tetracycline and novel antidepressants have been launched.

Pharmacology and Biochemistry

The mechanisms of action of antidepressants were of great importance for the theoretical understanding of the development of depressive diseases. It could be shown that antidepressants increase the concentration of the neurotransmitters norepinephrine and serotonin in the synaptic cleft. This is done either by inhibiting reuptake or by inhibiting enzymatic degradation.

Studies have shown that the neurotransmitters norepinephrine and serotonin are present in a disbalance or lowered in some of the depressive patients. The long-term application of antidepressants also leads to changes in the sensitivity of the postsynaptic receptors, in the sense of a β down regulation or 5-HT up regulation. This could also explain the clinical effect of antidepressants. The connections between the influenced transmitter system and the acute effect are not always clear. Imipramine seems to inhibit the reuptake of norepinephrine and thus contribute to an increase in propulsion.

In amitriptyline, on the other hand, the inhibition of serotonin reuptake is in the foreground, which seems to be responsible for the attenuating effect. Fluoxetine, however, is a selective serotonin reuptake inhibitor and does not have a sedative effect.

Tricyclic antidepressants

The name tricyclic antidepressants is based on their hydrophobic three-member ring system. The group of tricyclic and tetracyclic antidepressants has no selective affinity to a specific neurochemical transmitter system, but acts on the norepinephrine and serotonin system in other ways. They also act on peripheral receptors for acetylcholine and histamine. Typically, tricyclic antidepressants are classified according to their clinical-therapeutic profile.

Dual mechanism antidepressants
This group includes modern antidepressants whose mode of action is based on a serotonin and norepinephrine reuptake inhibition, a norepinephrine serotonin-specific effect or a dual-serotonergic effect.

Venlafaxine inhibits the reuptake of serotonin, norepinephrine and also dopamine. It is interesting to note that serotonin reuptake inhibition is predominant in the low dose range and norepinephrine reuptake is additionally blocked in higher doses. Therefore, high doses of venlafaxine are particularly suitable for the treatment of depression in combination with an anxiety disorder.

Mirtazapine inhibits central α2-noradrenergic receptors, which indirectly increases noradrenergic and serotonergic neurotransmission. On the other hand, a postsynaptic serotonin receptor antagonism causes an increased release of serotonin. Mirtazapine is traditionally taken before sleep, as it has a dampening effect and regulates the rhythm of sleep.

Substances: serotonin noradrenalin reuptake inhibitors: venlafaxine; serotonin noradrenalin-specific antidepressants: mianserin, mirtazapine.

Duloxetine a serotonin noradrenaline reuptake inhibitor with special position

Duloxetine is intended for a relatively specific indication, namely urinary incontinence in depressive women due to stress. The effect is based on influencing the onus nucleus in the sacral marrow, which is the area of origin of the motor fibres of the pudendal nerve.

Monoamine oxidase inhibitors

Monoamine oxidases catalyse the breakdown of neuroactive and vasoactive amines. Monoamine oxidase A deaminates norepinephrine, serotonin and dopamine, monoamine oxidase B deaminates phenylethylamine, benzylamine and dopamine. A distinction is made between irreversible nonselective and reversible selective monoamine oxidase inhibitors. The non-selective MAO inhibitors inhibit monoamine oxidase A and B and are particularly rich in side effects, so they should only be considered as the second choice.

Furthermore, the intake of tyramine must be restricted during ingestion, otherwise serotonin syndrome with fever, muscle twitching, hypertensive derailment, sweating, nausea and hallucinations may occur. Foods containing tyramine include chocolate, red wine, bananas and mature cheese, which is why they are called the cheese-effect. In the case of reversible MAO inhibitors, the symptoms caused by the intake of tyramine cannot be observed, as they only inhibit the monoamine oxidase A. The MAO inhibitors are also known as the cheese effect.

MAO inhibitors have a predominantly drive-increasing effect – not a mood-enhancing effect, which is why they are also called thymeretics. The area of indication is limited to depressions with a severe lack of drive and depression in old age.

General Psychopathology Factor May Describe Structure of Psychiatric Disorders

Mental disorders have traditionally been viewed as distinct categorical entities, but the high incidence of comorbid, or co-occurring, disorders challenges this view.

As researchers Terrie Moffitt, Avshalom Caspi, and colleagues observe in their new article in Clinical Psychological Science, about half of the people who meet diagnostic criteria for one disorder also meet the diagnostic criteria for another disorder at the same time.

“The high rates of comorbidity observed among mental disorders suggest that there may be a more parsimonious structure to psychopathology than implied by current nosologies that identify many separate and distinct disorders,” Moffitt, Caspi, and co-authors write.

To test this hypothesis, the researchers looked at longitudinal data collected from participants in the Dunedin Multidisciplinary Health and Development Study who were between the ages of 18 and 38. The researchers examined the participants’ mental health data, testing several possible statistical models to see which model best accounted for the data.

Confirmatory factor analysis revealed that the structure of mental disorders could be summarized by three core dimensions: an “internalizing” liability to depression and anxiety, an “externalizing” liability to antisocial and substance-use disorders, and a “thought disorder” liability to symptoms of psychosis.

Furthermore, analyses suggested that the propensity to develop any and all forms of common psychopathologies could be summarized by one general underlying dimension. Higher scores on this dimension, which the researchers call the “p factor,” were associated with greater life impairment, greater familiality, worse developmental histories, and more compromised brain function in early life.

“We propose that p influences present/absent performance on hundreds of psychiatric symptoms, which are typically aggregated into dozens of distinct diagnoses, which further aggregate into two overarching Externalizing versus Internalizing domains, which finally aggregate into one normally distributed dimension of psychopathology from low to high: p,” the researchers conclude.

One way to think about the p factor is in relation to the structure of cognitive abilities:

“These abilities are dissociable into separate abilities, such as verbal skills, visuospatial skills, working memory, or processing speed,” say the researchers. “Nonetheless, the general factor in intelligence (called the g factor) summarizes the observation that individuals who do well on one type of cognitive test tend to do well on all other types of cognitive tests.”

While there are specific factors that account for variation in each test, the g factor accounts for the positive correlation among all test scores, suggesting that there may be a common etiology that influences or contributes in some way to all cognitive functions.

The new findings suggest that, just as there is a general factor of cognitive ability, there may also be a general factor of psychopathology. This general factor may, in turn, help to explain why researchers have had difficulty finding distinct causes, biomarkers, and treatments for individual mental disorders.

Moffitt, Caspi, and colleagues hope that these initial findings generate “further tests, extensions, and discussions about the structure of common mental disorders.”