Benperidol, Chlorpromazine, Flupenthixol, Fluphenazine, Haloperidol, Levomepromazine, Pericyazine, Perphenazine, Pimozide, Prochlorperazine, Promazine, Sulpiride, Trifluoperazine, Zuclopenthixol
Neuroleptic medications may be prescribed to individuals deemed to be having 'psychotic' experiences e.g. hearing voices others do not hear, seeing things others do not see, strongly holding beliefs others believe to be abnormal, developing paranoid ideas etc. The typical neuroleptics differ from the atypical neuroleptics in that they in the majority of individuals induce more extra-pyramidal side effects (see later for explanation of term) and have an increased effect on a hormone called prolactin (again, see later for explanation of relevance).
They may be prescribed in the short term in order to quieten 'disturbed' individuals, to individuals given a diagnosis of Schizophrenia, individuals deemed to be manic, individuals who have 'psychotic' experiences whilst depressed, individuals with severe anxiety, individuals who have suffered brain damage or are in a state of toxic delirium.
Neuroleptic medications are also sometimes referred to as 'anti-psychotic' medications. However, we believe this term to be misleading implying that the drugs specifically affect 'psychotic' symptoms, but this is not the case. Some individuals who have psychotic experiences find the drugs of no benefit to them, for others the side or adverse effects of the drugs strongly outweigh any beneficial effects the drugs may be having. But some individuals do find these medications useful.
The theory behind why individuals develop 'psychotic' symptoms is based upon the idea that there are elevated levels of dopamine in the brain. Dopamine is a neurotransmitter, a molecule that passes messages between neurons. For example, when a nerve impulse arrives at a dopaminergic neuron (also known as a pre-synaptic neuron), dopamine is released from the cell and diffuses through a space between two neurons, called the synaptic cleft. Dopamine then binds to specific dopamine receptors on a different neuron (post-synaptic neuron) producing a specific signal, impulse or effect. Dopamine is then released from its receptors and 're-absorbed' into the pre-synaptic neuron, or degraded by enzymes in the synaptic cleft.
The neuroleptics block dopamine receptors thereby inhibiting the ability of dopamine to attach to these receptors and generate signals. However, unlike the atypical neuroleptics, the typical neuroleptics permanently block the receptors therefore allowing very little, if any, dopamine to bind to the receptors and generate signals. However, the typical drugs differ in their 'stickyess' when binding to dopamine receptors. This may result in some typicals producing higher levels of specific adverse effects than others. The typicals may also bind to other receptor types, producing further adverse effects (see side effects of typicals section).
The body will always try to maintain itself in a state of optimal conditions for cell functioning. Therefore if a drug is introduced that blocks a specific signal or function the body will try to compensate for this. So, if an atypical neuroleptic blocks dopamine receptors, the cell on which the receptors are located will sense that it is not receiving as many signals from the dopamine receptors as it used to. In the long term, the cell will respond by producing more receptors, in an attempt to get the level of dopamine receptor signalling it is used to. As well as producing increased numbers of dopamine receptors, the sensitivity of the dopamine receptors is increased. If an individual then decided to abruptly discontinue taking the atypical neuroleptic, the dopamine receptors would no longer be blocked and fully exposed. So should anything potentially exciting or stimulating happen, dopamine would be released and bind to the increased numbers of extra sensitive receptors, leading to increased dopamine transmission, over and above what would have occured before the atypicals were introduced. In this scenario, some individuals develop 'psychotic' symptoms, due to over flooding of dopamine receptors, which may be interpreted as a 'relapse'.
The development of psychotic symptoms when there is excess dopamine transmission (as may occur in abrupt withdrawal) may lead some individuals to believe that increased dopamine signalling may have been responsible for the psychotic experiences an individual initially had when the drugs were first prescribed. However, individuals who had no psychiatric history have been given a course of neuroleptic treatment, and when the neuroleptics were abruptly withdrawn some of these individuals developed 'psychotic' symptoms.
Neurons that secrete dopamine are primarily located in three discreet regions of the brain; substantia nigra, ventral tegmental area and the hypothalamus and pituitary. It is theorised that there is excess dopamine secreted from the neurons in the ventral tegmental area which send signals from the midbrain to the cortex and limbic regions of the brain. However, the typicals do not specifically target the dopaminergic neurons in the ventral tegmental area, they affect all dopaminergic neurons. They also interfere with other receptor subtypes found on neurons including; adrenergic, histaminergic and muscurinic receptors, all of which when interfered with can produce adverse effects to the individual taking the drug.
To describe the side or adverse effects, it is easier to do it by looking at the brain regions in which dopamine receptors are found and look at the adverse effects created which are due to drug induced changes in these regions. The adverse efffects that may occur through the neuroleptics interactions with other neurotrasmitter/receptor systems will then be described followed by the drug specific side effects that are most commoly reported.
Parkinsonism: The neurons found in the /substantia nigra/ are involved in the initiation of muscular planning, and muscle co-ordination (e.g. walking). The major neurotransmitter co-ordinating the neurons in this region is dopamine. Therefore when neuroleptics block dopamine receptors/signalling, this can result in problems with co-ordination and movement. Individuals may develop a tremor, most commonly of the hand, stiffness and lack of or slowing of movement, difficulty initiating movement (e.g. rising from a chair). If the facial muscles are affected, individuals may appear expressionless, blank, may drool and there may be a slowing of or delay in speech. Abnormal movements tend to affect the hands and arms but the legs may also be affected. The respiratory muscles may also be involved, they can become disco-ordinated in their contractions which may result in breathlessness or wheezing. This can occur persistently or episodically (e.g. only at night). These effects can be reversed upon withdrawal of or a reduction of the neuroleptic.
Akathisia: This is a state of highly unpleasant physical and psychological restlessness. Many individuals may find it difficult to sit still and feel like they literally want to jump out of their skin. However, to an outsider observing there may be no noticeable discomfort. Individuals may feel extreme mental turmoil, feel strange 'unlike themselves', paniciky or experience strange or unusual impulses. As neuroleptics are supposed to reduce irritability and impulsivity an individuals expression of these experiences may not be taken seriously, however, these are definite side effects of neuroleptics and should be taken seriously.
Dystonia: Dystonia basically refers to when a muscle has gone into spasm. Virtually any muscle can be affected but the most commonly affected include the muscles of the mouth, eyes and jaw. When the mouth or larynx are affected individuals may find speaking, eating or drinking difficult, there may also be changes in the tone of the voice. When the eyes are affected the eyeballs may appear to roll up into the head so that only the whites of the eyes can be seen. These spasms can be reversed by neuroleptic discontinuation or with the institution of an anti-cholinergic drug (e.g Procyclidine). The jaw can become locked or clench abnormally for periods of time which can lead to dental problems. Muscle spasms can be very painful, and may be misdiagnosed as pain syndromes in the affected muscle regions.
Tardive dyskinesia: This term refers to a delayed (hence tardive) onset of abnormal movements of the face and mouth, but can also affect the muscles of the trunk and limbs and usually occurs after months or years of taking neuroleptics. Unlike other adverse effects of neuroleptics affecting the muscles, tardive dyskinesias may last for several months or years after the neuroleptic has been discontinued and anti-cholinergic drugs do not appear effective in reversing these effects. However, there is evidence suggesting that clozapine and quetiapine may be beneficial in supressing the dyskinesia. Involuntary movements of muscles of the mouth and tongue may look like lip smacking movements, protrusion of the tongue, grimacing and chewing movements. An association has been noticed between dose of neuroleptic and increased risk of developing tardive dyskinesia, however it has developed in individuals exposed to lower doses of neuroleptics for short periods of time.
Parkinsonism, Akathisia, Dystonias and Tardive Dyskinesia are commonly reffered to as Extra Pyramidal side effects (EPSE's). They are less commonly occuring in atypical neuroleptics when compared to the typical neuroleptics, however they do occur especially when high doses of atypicals are used. It is for this reason that they have been included under atypicals.
Demotivation: Dopamine also has important roles in neuronal signalling in the regions of the brain thought to be responsible for motivation and the gaining of rewards, the ventral tegmental area, containing dopamine signalling mesolimbic and mesocortical pathways. When the neuroleptics block dopamine receptors and hence reduce dopamine signalling in these areas, individuals may feel de-motivated or experience a state of 'in-difference'. Indifference has been refered to as a 'who cares' type of feeling, there is no real desire to do anything. This can be misinterpreted by mental health workers as the development of 'negative symptoms' in individuals who have been given diagnoses of Schizophrenia. Individuals also report feeling emotionally blunted, unable to feel anger, joy, contentment. This may affect individuals abilities to form relationships, search for employment, engage in social activities. It can be difficult to distiguish indifference and apathy from depressive demotivation or just life itself. Some individuals who develop these experiences can often be prescribed anti-depressants in an attempt to lift an individual, however, if the neuroleptics are the cause, anti-depressants will not necessarily help.
Dopamine also has important roles in neuronal signalling between the hypothalamus and pituitary gland, the tuberoinfundibular pathway. In the pituitary gland dopamine binds to dopamine receptors, which causes a decrease in the amount of prolactin released into the bloodstream. When neuroleptics block dopamine receptors in the pituitary, there is no longer any inhibitory factors controlling prolactin secretion, therefore relative prolactin secretion is increased. Prolactin functions in the body to increase breast size and milk production in mothers who have recently given birth. However, in individuals taking neuroleptics (except clozapine and quetiapine) raised prolactin secretion can lead to enlargement of the breasts (in both sexes) and an increase in milk production and secretion from the breasts. Raised prolactin levels may also interfere with a females menstrual cycles, causing irregular periods or stopping periods altogether (amenorrhoea).