Psychiatric medications (psychopharmacology) part III

Psychiatric medications (psychopharmacology) part III 

Typical anti-psychotics 

Among the typical antipsychotics the important are chlorpromazine, trifluperazine, fluphenazine, thioridazine, haloperidol, pimozide, thiothxine, loxapine, sulpiride and amisulpiride etc. are useful. Some doctors prefer one medication than the others.  

How medications act on the brain and other body systems? 

In our brain we have different receptors in nerve cells in different parts of brain. The different receptors acted on by different neuro-chemicals, also known as neuro transmitters. Some of these are dopamine, histamine, acetylcholine etc. These neuro-transmitters are synthesized in the nerve cells and other cells from their respective different amino acids and other chemicals. After synthesis those neurotransmitters are stored in the nerve cells, and released when necessary. 

It is hypothesized that dopamine is found in high concentration in some areas of brain in psychosis. So typical antipsychotics when it reaches brain, there it attaches to the dopamine receptors to prevent the action of dopamine on the receptors. Thus it reduces psychosis, by controlling the agitation, aggression, hallucination and delusion.  

The typical antipsychotics also act on different other receptors such as histamine and acetylcholine in the brain and other organs thus causing side effects of medications. Also blockage of dopamine receptors cause some other side effects such as tremor, rigidity or stiffness of muscles and limbs, excess salivation etc. this side effect is known as parkinsonian as it is similar to patients suffering from parkinsonism.     

Because of blocking histamine receptors in brain typical antipsychotics cause sleepiness, and blocking acetylcholine receptors it causes dry mouth and constipation. These medications also cause act on adrenergic receptors thus causing low blood pressure and increased heart rate.  

It was also found that medications block the receptors immediately but the patients improve only after few days of treatment, and also that when medications are discontinued patients do not become unwell immediately, and it takes few weeks to few months. From this observation it can be said that we still don’t know how the medications work to treat the psychosis. 

What are the conditions can be treated? 

1)     Schizophrenia: it can be treated by any of the typical antipsychotics mentioned above. But the doses vary according to weight, or when some other medications are taken by the patient, and age.

2)     Any other psychoses characterized by delusions, hallucinations, and mania characterized by high mood, agitation, aggressive behaviour, and grandiose delusions.

3)     Any severe agitation or violent behaviour also treated or controlled by typical antipsychotics. Usually haloperidol, chlorpromazine, trifluperazine, and others also may be used.

4)     Any psychosis due to other medical conditions such as in dementia, or due to drug abuse can be treated or controlled by these medications. Mostly doctor use haloperidol, chlorpromazine, or trifluperazine, etc.  

Side effects of typical antipsychotic medications:   

1)     Sudden death: This is due to effect on heart and Thioridazine is the important one to cause it. There have been reports of patients died due to taking Pimozide and Clarithromycin together and so this type of combination should be avoided.

2)     Postural hypotension: This is a common side effect when patients feel dizzy and may even fall on standing, more common in elderly patients. Patients should be advised not to stand abruptly. They sit at the edge of bed for a few minutes then stand slowly. If they feel dizzy again then they may lie down. Patients should not take coffee and drink more water and salt unless having high blood pressure. It usually passes of after few days of treatment.

3)     Sleepiness: This is common with most typical antipsychotics. Much severe with chlorpromazine, thioridazine etc. with continued use sleepiness becomes less and less.

4)     Tremor and acute rigidity: This happens usually when medications are started for the first time. Patients may recover from these side effects in next couple of months, and some patients may require medications to counteract it for indefinite time. This cause many patients to stop medications. 

5)     Dry mouth: This is common, patients suck lozenges or any chewing gum. Drinking water does not help but taking small sips of water keep mouth moist for few minutes.

6)     Constipation: This can be treated by laxatives and diet modification such as advising to take more vegetables or roughage in diet.

7)     Urinary retention: This is common in old age and when patients are given medications for side effects such as for tremor and rigidity etc. 

8)     Endocrine effects: this is due to increased secretion of Prolactin, which causes breast enlargement in men, and secretion of milk in women, lack of menstruation, impotence and lack of libido.

9)     Sexual side effects: This is common with most psychiatric medications. Most common complaint is loss of sexual desire, lack of sexual satisfaction or lack of orgasm.

10) Weight gain: This is also common and is due to increased appetite, poor motivation to any activity.

11) Other uncommon side effects: Allergic dermatitis occurs in patients taking chlorpromazine, commoner in patients with European origin. Thioridazine is associated with pigmentation of retina when given in a higher dose (more than 800mg). It may cause blindness if the medication is continued further. This is not reversible so it can be prevented by stopping the medication. Chlorpromazine also causes pigmentation of retina but it does not affect the vision. Jaundice occurs in early part of treatment with chlorpromazine. Then medication should be discontinued immediately. 

Another important aspect of treatment is drug-drug interaction, drug with alcohol interaction are not discussed here. This should be discussed with the prescribing doctor. 

What are the doses?   

The doses of different medications vary and it depends on the weight, age, condition of the patient, any associated physical illness or any organ damage such as any liver and kidney or any heart problem.  

Ethnicity also needed to be taken into account. Asian patients found to tolerate medications less than European patients so less medication dose is given.  

Doses also vary according to route of administration such as by mouth more medications are needed than by intramuscular injection or by intravenous injection. Depot injection doses also vary and doctors usually prescribe an average dose, according to response the doses are adjusted.  

So in regard to doses the warning is that patients need to keep in touch with prescribing doctors and the medication dose needed to be reviewed at frequent intervals until condition of the patient settled down.  

To minimise the side effects doctors at times change the medication or reduce the dose, and in the process of change there may be deterioration of mental condition and so patients may observed closely. 

Most medications interact with alcohol, other illicit drugs, with other medications, even with over the counter medicines such as cough syrup etc. So this should be discussed with the doctor before they make any change. 

The doses of medications are not discussed here and it should be discussed by the patient and their family with the prescribing doctor. 

Atypical antipsychotic medications  

These are different than typical antipsychotics as they block the dopamine and serotonin receptors in brain. These have less side effects such as less tremor, less chances of rigidity, but these cause more weight gain, and clinicians believe that these are better antipsychotics and patients continue to have it for longer period of time.  

How the atypical antipsychotics work? 

These medications block the dopamine receptors and serotonin receptors both. The action on serotonin receptors are more than dopamine receptors, thus it causes less tremor and rigidity and other neurological side effects.  It has been noted that these medications have more effects on some symptoms of schizophrenia such as withdrawal, apathy, also on hallucination, delusion, agitation etc. 

Side effects of atypical antipsychotics These medications have some unique side effects. In general these cause lesser side effects than typical ones.  Serious side effects in blood: This is not uncommon in patients taking Clozapine. It may cause reduction of white blood cell (WBC) which helps in combating infection. This reduction of WBC when becomes too low, patients may present with fever, sore throat and other infections. Then medication must be stopped immediately and send the patient to emergency. Some patients have died due to severe infection as WBC count did not recover after medication discontinued. So patients taking clozapine must have monthly regular blood tests to check the WBC count and have regular follow up by a psychiatrist. If a patient taking clozapine has any infection or fever or sore throat they must see their doctor immediately.  

Other side effects as found in typical antipsychotics: Clozapine cause too much sleepiness or sedation and this may reduce on ongoing use. There may be dizziness due to lowering of blood pressure, Patients complaint of excess salivation and they may wet their pillow due to this. Constipation is also common.It may increase heart rate and lower blood pressure.

Weight gain is important and is common with clozapine, Olanzapine, risperidone, quetiapine etc. Too much increase in weight may lead to diabetes and high cholesterol. So monitoring of weight is important and encourage dieting and exercise.  

Among all the atypical antipsychotics risperidone causes more endocrine changes. Thus it may cause high level of Prolactin hormone in body leading to lack of menstruation in women, enlargement of breast in men, loss sexual desire etc. 

Clozapine, like atypical antipsychotics may cause epileptic fits in epilepsy patients.  Thus it should be treated by stopping clozapine and starting a medicine for epilepsy and then clozapine may be started again.  

What are the atypical antipsychotics? 

Clozapine, Olanzapine, risperidone, quetiapine, sertindole, Ziprasidone 

What are the uses of atypical antipsychotics? 

Most of the atypical antipsychotics are used in the treatment of schizophrenia or in psychosis.

Clozapine is used only in treatment of schizophrenia which is resistant to other antipsychotic medications.  

Among the above only risperidone is found in long acting injection form.

Olanzapine is available in short acting injection which is used in acute psychotic conditions.    

Medications in India 

Medication dispensing and selling in India is a bit different than other developed countries where there are strict laws which control selling or dispensing of psychiatric medications.  Patients and their families buy medicines from the pharmacy shops, sometimes with an old prescription and patients were not seen or reviewed by doctors recently.

This is common due to: 

1)     Lack of understanding of the mental illness and it’s treatment plans as it happens in most other countries and cultures.

2)     Often patients refuse to see a doctor due to poor insight (this means patients has no understanding that they are suffering from any mental illness)

3)     Patients and family believe that patient is doing ok and so there is no need for check up.

4)     Patients and the family may not have money to pay consultation fee to the private doctors, thus avoid any review. This can be avoided if a patient visits a public hospital where treatments and medication are free.  

Pharmacists sell medications to patients without any proper prescription. There has been little control by the drug control inspectors of the prescription medications. Even sedatives such as Lorazepam, diazepam, and anxiety medications such as Alprazolam, etc are sold to the patient without proper prescription.  

Due to use of above medications without any medical supervision patients tend to abuse those drugs and may become dependent on such medications. Also it causes more chances of drug overdose or suicidal attempts. 

Some of the psychiatric drugs are prescribed by general practitioners and other specialists and even by non qualified medical practitioners in rural and semi urban areas. This may cause unnecessary and unsafe use of medications and without or little effects on the mental condition of the patient.  

Many brand names of any psychiatric medications is another problem. This makes difficult for the clinicians which one to choose in regard to usefulness, quality etc.

There are very few medications, specially psychiatric medications available in generic names. Generic medications are available in free government pharmacies where most of the medications are bought by tenders.    

Fixed dose combinations   

There have been a lot of issues with the fixed dose combination of psychiatric medications.

In favour of fixed dose combination:

This is useful, as some clinicians and manufacturers say that it ensures compliance, less number of pills to take, probably less cost of treatment. In countries like in India it is easier to manage the patient by fixed dose combination. 

In against of fixed dose combination:

Patients takes unnecessary medication when not required. As for example, fixed dose combination of Trifluoperazine and benztropine used in treatment of schizophrenia and other psychosis. Patients may not need Benztropine after some times when there would be no side effects. So if patient continues to take the combination tablets then they will be taking extra benztropine. Taking fixed dose combinations of trifluoperazine and benztropine is costlier than taking only trifluoperazine.  

In the Indian medicine market there are many fixed dose combinations such as: Haloperidol with benzhexol; Trifluoperazine with benzhexol; amitriptyline with chlordiazepoxide; Olanzapine with Fluoxetine; these are found in different dose combinations. None of these combinations are available in western medicine markets except Olanzapine and Fluoxetine combination.   

It is important to remember that the side effects which are mentioned above with different medications do not happen all with every patient. Many patients may have few side effects, some side effects are insignificant and patients become used to it, while others lessens over time. There is no medication without any side effects in available at present.