Psychopharmacological agents – a cure or a trap?
Neuroleptics - a long known poison
Neuroleptics, or anti-psychotics, have been always been accepted as the cure for the psychoses, among other off label uses. What one would expect from neuroleptics is to attenuate both the negative (affective) and positive (psychotic) symptoms of the disorders, such as schizophrenia, turning the patient into a highly functioning, sane citizen once again. After all, they are called anti-psychotics so common sense dictates that they work against psychosis. Nevertheless, the real situation could not be farther from the truth.
If we, again, look at the medication from a pscycho-pharmacological perspective we are left to draw unexpected conclusions. Therefore lets look at dopamine, again a single neurotransmitter which receives almost all the blame for the variable disorder. Haldol, risperidone, olanzapine and any other first or second generation anti-psychotic act majorly as dopamine receptor antagonists (D2 majorly). After the drug is administered and once it or its metabolites cross the blood brain barrier binding at the corresponding post-synaptic receptors occurs, preventing the elicitation of the usual physiological response. Hyperactive firing of these post-synaptic dopamine receptors is being used as the arbitrary claim for causing the psychotic symptoms thus slowing the firing should alleviate the psychosis. Be it as that may, the brain begins soon to compensate. Post-synaptic receptors sense a lowered activity and respond by surfacing more receptors hoping to raise the chance of transmitter-binding and so increase the net firing rate. Additionally, the drug binds to the feedback autoreceptors on the pre-synaptic neuron increasing either transmitter synthesis or release or both. The dopamine receptors have successfully been hyper-sensitized, laying the groundwork for a heightened chance of relapse if the medication is discontinued.(2) Behaviorally, the patient seems to stabilize, at least in the short-term, under the influence of medication, and because his/her dopamine receptor become super-sensitive with continued use abstaining from the drug will likely precipitate another psychotic episode. Unfortunately, many tend to make the wrong connections, to the advantage of the pharmaceutical companies synthesizing the drug, and blame the relapse on not abiding to the prescribed medication regimen, albeit the medication itself is directly responsible. The delusion has been born. The result of this maladaptive approach is turning what could have been a temporary psychosis into a perennial problem, hindering any hopes for a favorable prognosis - integration back into the society becomes an unattainable dream.(3)
As if it were not sufficient already, neuroleptics begin to further degenerate the patient's life as their use continues. The side effects of neuroleptics include many irritating symptoms such as lethargy, weight gain, dry mouth and restlessness, none of which convey a feeling of recovery or complacence. Furthermore, the sensitization of the dopaminergic system in neuroleptic users has been associated with development of tardive dyskinesia, manifested as bodily tics, which is often irreversible indicating permanent damage.(1) What is the antidote to tardive dyskinesia? The answer is more neuroleptics. This is why it can be hard to detect if the patient is committed to the medication, as the drug is masking the symptoms it is causing. To everyone's surprise this is not a novel discovery as the study on which I am basing majority of this text is over three decades old. Thirty years is more than enough time for the information to have spread yet it failed to do so.
References:
(1) - Am J Psychiatry 135:11, November 1978:
Another implication is the possibility that this super-sensitivity is irreversible. This is accepted to be true of tardive dyskinesia unless it is diagnosed early and medication is discontinued. If the same irreversibility is occuring in the mesolimbic region, the result would be patients who must remain on neuroleptics for the rest of their life regardless of the natural course of their illness.
(2) - Am J Psychiatry 135:11, November 1978:
In the studies done by Hogarty's group, two thirds of patients thought to be suitable for drug withdrawal after 2 years of drug therapy relapsed following drug discontinuation, causing the authors to state that "the need for maintenance chemotherapy may be indefinite. In some of these cases, the need for continued neuroleptic treatment may itself be drug-induced.
(3) - Am J Psychiatry 135:11, November 1978:
We suggest that neuroleptics can produce a dopamine supersensitivity that leads to both dyskinetic and psychotic symptoms.
Neuroleptics, or anti-psychotics, have been always been accepted as the cure for the psychoses, among other off label uses. What one would expect from neuroleptics is to attenuate both the negative (affective) and positive (psychotic) symptoms of the disorders, such as schizophrenia, turning the patient into a highly functioning, sane citizen once again. After all, they are called anti-psychotics so common sense dictates that they work against psychosis. Nevertheless, the real situation could not be farther from the truth.
If we, again, look at the medication from a pscycho-pharmacological perspective we are left to draw unexpected conclusions. Therefore lets look at dopamine, again a single neurotransmitter which receives almost all the blame for the variable disorder. Haldol, risperidone, olanzapine and any other first or second generation anti-psychotic act majorly as dopamine receptor antagonists (D2 majorly). After the drug is administered and once it or its metabolites cross the blood brain barrier binding at the corresponding post-synaptic receptors occurs, preventing the elicitation of the usual physiological response. Hyperactive firing of these post-synaptic dopamine receptors is being used as the arbitrary claim for causing the psychotic symptoms thus slowing the firing should alleviate the psychosis. Be it as that may, the brain begins soon to compensate. Post-synaptic receptors sense a lowered activity and respond by surfacing more receptors hoping to raise the chance of transmitter-binding and so increase the net firing rate. Additionally, the drug binds to the feedback autoreceptors on the pre-synaptic neuron increasing either transmitter synthesis or release or both. The dopamine receptors have successfully been hyper-sensitized, laying the groundwork for a heightened chance of relapse if the medication is discontinued.(2) Behaviorally, the patient seems to stabilize, at least in the short-term, under the influence of medication, and because his/her dopamine receptor become super-sensitive with continued use abstaining from the drug will likely precipitate another psychotic episode. Unfortunately, many tend to make the wrong connections, to the advantage of the pharmaceutical companies synthesizing the drug, and blame the relapse on not abiding to the prescribed medication regimen, albeit the medication itself is directly responsible. The delusion has been born. The result of this maladaptive approach is turning what could have been a temporary psychosis into a perennial problem, hindering any hopes for a favorable prognosis - integration back into the society becomes an unattainable dream.(3)
As if it were not sufficient already, neuroleptics begin to further degenerate the patient's life as their use continues. The side effects of neuroleptics include many irritating symptoms such as lethargy, weight gain, dry mouth and restlessness, none of which convey a feeling of recovery or complacence. Furthermore, the sensitization of the dopaminergic system in neuroleptic users has been associated with development of tardive dyskinesia, manifested as bodily tics, which is often irreversible indicating permanent damage.(1) What is the antidote to tardive dyskinesia? The answer is more neuroleptics. This is why it can be hard to detect if the patient is committed to the medication, as the drug is masking the symptoms it is causing. To everyone's surprise this is not a novel discovery as the study on which I am basing majority of this text is over three decades old. Thirty years is more than enough time for the information to have spread yet it failed to do so.
References:
(1) - Am J Psychiatry 135:11, November 1978:
Another implication is the possibility that this super-sensitivity is irreversible. This is accepted to be true of tardive dyskinesia unless it is diagnosed early and medication is discontinued. If the same irreversibility is occuring in the mesolimbic region, the result would be patients who must remain on neuroleptics for the rest of their life regardless of the natural course of their illness.
(2) - Am J Psychiatry 135:11, November 1978:
In the studies done by Hogarty's group, two thirds of patients thought to be suitable for drug withdrawal after 2 years of drug therapy relapsed following drug discontinuation, causing the authors to state that "the need for maintenance chemotherapy may be indefinite. In some of these cases, the need for continued neuroleptic treatment may itself be drug-induced.
(3) - Am J Psychiatry 135:11, November 1978:
We suggest that neuroleptics can produce a dopamine supersensitivity that leads to both dyskinetic and psychotic symptoms.