Drug therapy: typical and atypical antipsychotics

DRUG THERAPY: TYPICAL AND ATYPICAL ANTIPSYCHOTICS.

The Biological Approach explains mental disorders in terms of abnormalities of the central nervous system, i.e. that there is something wrong with the workings of the brain. For example, Schizophrenia has been explained as being caused by an excess of the neurotransmitter dopamine. Drugs that alter dopamine levels supposedly block receptor sites, inhibiting reuptake and improving the breakdown of molecules following release.

KEY TERMS

MEDICATIONS ALSO KNOWN AS CHEMOTHERAPY: Drug treatments

Neurotransmitter: A neurotransmitter, is a chemical that allows neurons in the brain to communicate, they do this by producing a bridge across the synapse between the axon terminals and dendrites; this process allows the continuation of the nerve impulse to progress.

DOPAMINE:  a neurotransmitter.

DOPAMINE FUNCTION:  Dopamine has many functions in the brain, including important roles in behaviour and cognition (thinking), voluntary movement, motivation, punishment and reward, pleasure, and focus.

PSYCHOTROPIC DRUGS: A psychotropic describes any drug that affects behaviour, mood, thoughts, or perception. It’s an umbrella term for a lot of different drugs, including prescription drugs and commonly misused drugs.

PHARMACEUTICAL PSYCHOTROPIC DRUGS: Types of legal, prescription, psychotropic medications. There are five main types of psychotropic medications: antidepressants, anti-anxiety medications, stimulants, antipsychotics, and mood stabilizers.

ILEGAL PSYCHOTROPIC DRUGS, e.g., street drugs: crack-cocaine, amphetamines (speed), cannabis, Lysergic acid diethylamide (LSD); Phencyclidine (PCP or angel dust); Psilocybin (magic mushrooms); heroin; (Methylenedioxymethamphetamine (MDMA or Ecstasy); Methamphetamine (crystal meth) etc.

AGONIST/STIMULANTS are drugs that increase the availability of a neurotransmitter in the brain. There are many illegal agonists, e.g., street drugs: cocaine, crack, and PCP. LSD, amphetamines (speed), ecstasy cannabis, heroin, and crack etc. Legal agonists are L-dopa, methadone, Prozac, and Valium. L-dopa is often used in Parkinson’s patients to increase dopamine availability in the brain.

ANTAGONIST/BLOCKERS drugs that block the availability of a neurotransmitter in the brain. There are not any street drugs that do this. Antagonists used to block dopamine are known as antipsychotics, and neuroleptics (phenothiazines such as chlorpromazine (Thorazine), risperidone and clozapine are some examples.

ANTIPSYCHOTICS: Drugs that reduce Neurotransmitter availability, e.g. Antagonists or Blockers.

NEUROLEPTICS: Another name for Antipsychotics. There are subtle differences between Neuroleptics and Antipsychotics, e.g. on which Dopamine receptors they work D1, D2, D3 etc.  If you are interested in ‘Google’ what’s the difference between them, AQA will be very impressed if you know D1, D2 etc. Don’t worry if you are confused enough already, you can impress AQA in other ways.

TYPICAL ANTIPSYCHOTIC DRUGS: Conventional Antipsychotics (1950’s) that reduce Dopamine only. Also they usually only reduce positive symptoms. They are very likely to cause the side effect of Tardive Dyskinesia in 20-30 % of users.

AtTYPICAL ANTIPSYCHOTIC DRUGS:  Newer Antipsychotics (1990s) that reduce Dopamine and Serotonin. Also, they reduce positive and negative symptoms. They are much less likely to cause the side effect of Tardive Dyskinesia. Although more likely to cause Agranulocytosis.

HYPO AND HYPER-: These two prefixes are easily confused as they sound similar, but they have, in fact, more or fewer opposite meanings. Hyper- means over, excessive, more than normal, as in such words as hyperbole (extravagant and obvious exaggeration) and hyperactive (abnormally or pathologically active). Hypo means low, under, beneath, down, or below normal, as in hypoglycaemia (low blood sugar) and hyposensitivity (under sensitivity). Regarding neurotransmitters, a hyper neurotransmitter system means too much neurotransmitter is being secreted into the synapses within a certain neural circuit. Because of this, it produces over-stimulation of the cells and causes an exaggeration of functions. Agonists: Drugs that increase Neurotransmitter availability, e.g. stimulants.

TARDIVE DYSKINESIA: is a difficult-to-treat form of Dyskinesia (disorder resulting in involuntary, repetitive body movements) that can be Tardive (having a slow or belated onset). It frequently appears after long-term or high-dose use of typical antipsychotic drugs. Tardive Dyskinesia is characterized by repetitive, involuntary, purposeless movements, such as grimacing, tongue protrusion, lip-smacking, puckering and pursing of the lips, and rapid eye blinking. Rapid movements of the extremities may also occur. Impaired movements of the fingers may also appear. For comparison, patients with Parkinson's disease have difficulty moving, while patients with Tardive Dyskinesia have difficulty not moving.

AGRANULOCYTOSIS:  A lowered number of white blood cells (remember these are vital for fighting infection and made in the bone marrow. Agranulocytosis may be asymptomatic, or it may clinically present with sudden fever, rigours and sore throat. Infection of any organ may be rapidly progressive (e.g., pneumonia, urinary tract infection). Septicaemia may also progress rapidly. Neutrogena and Agranulocytosis are associated with gum diseases, such as gingival bleeding, saliva increase, halitosis, osteoporosis, and destruction of periodontal ligament Causes: Many drugs have been associated with Agranulocytosis, including some antipsychotics (the atypical antipsychotic Clozapine. Clozapine users in the US must be nationally registered to monitor low white blood cell counts.

NEUROLEPTIC MALIGNANT SYNDROME: (NMS) is a life-threatening neurological disorder most often caused by an adverse reaction to Neuroleptic or Antipsychotic drugs. It generally presents with muscle rigidity, fever, autonomic instability, and cognitive changes such as delirium, and is associated with elevated Creatine Phosphokinase (CPK). The incidence of the disease has declined since its discovery (due to proactive prescription habits), but it is still dangerous to patients being treated with antipsychotics. Because of its unpredictability, there is no one set course of action to treat the syndrome, but generally, removal of the antipsychotic drug treatment, along with medical management, leads to a positive outcome.

TYPICAL ANTIPSYCHOTICS 1950’S

Antipsychotics were discovered accidentally after it was found that giving patients antihistamines before surgery reduced surgical shock by making patients more sleepy and less fearful about their impending operations. This breakthrough finding encouraged pharmaceutical companies to re-examine antihistamines and find out why they had tranquilising effects.

Research soon showed that it was the nucleus of the antihistamines (phenothiazine) that was causing this sedative effect in patients.  Shortly thereafter, the French chemist Paul Charpentier prepared a new phenothiazine derivative, which he called Chlorpromazine; thus, the first typical antipsychotic was created.

At first, Chlorpromazine was given to a variety of patients who had disturbed and agitated behaviour, but it was soon discovered that it was very effective in calming patients with Schizophrenia and psychosis. 

As Phenothiazines derive their therapeutic properties by blocking dopamine receptors in the brain, it was hypothesised that Schizophrenia might be caused by excess Dopamine. As a result, the original Dopamine hypothesis was born.

The dopamine hypothesis of schizophrenia is a theory that argues that the unusual behaviour and experiences associated with schizophrenia (sometimes extended to psychosis in general) can be fully or largely explained by hyperactivity of dopamine D2 receptor neurotransmission in subcortical and limbic regions of the brain. This is because excess Dopamine has a profound influence on thought, feelings and behaviour. 

Dopamine is a neurotransmitter, meaning that it is a chemical that allows two neurons in the brain to communicate, produces a bridge across the synapse between two cells and allows the continuation of the nerve impulse to progress. So, the dopamine hypothesis of schizophrenia basically says that the symptoms of schizophrenia, principally the hallucinations, the delusions, and the psychosis, are the result of too much dopamine being active in the brain, e.g., being secreted into the synapses within a certain neural circuit. And because of this, it produces this over-stimulation of the cells and these symptoms.

According to Kapur, dopamine inflames the cognitive tendencies that people with schizophrenia exhibit even before they become ill. He says: ‘If you could test patients before they were psychotic, you’d probably find they tend to jump to conclusions or choose extreme explanations. When you add to this a biochemical fuel – excess dopamine – you inflame this way of thinking. That is what dopamine does. The antipsychotic drugs douse the flames and take away the fuel – they do not fundamentally change the patients’ tendencies, and that’s why relapse usually occurs when medication is stopped. One of the reasons that we know this is the case is because often, people who have not had the illness will experiment with drugs like cocaine, or amphetamine, or methamphetamine, drugs that stimulate the release of dopamine in the brain. Their experimenting and taking these medications will precipitate the onset of the illness and will trigger the symptoms of the illness.

THORAZINE (CHLORPROMAZINE)

The first antipsychotic, Chlorpromazine, was officially introduced in 1954, but by 1970, more than 85 per cent of all patients in state mental hospitals were receiving the drug. As phenothiazines derive their therapeutic properties by blocking dopamine receptors in the brain, it was hypothesised that schizophrenia might be caused by excess dopamine.

Typical antipsychotics are primary medications for treating excess Dopamine in Schizophrenia. Typical antipsychotics (also known as Conventional antipsychotics) are all supposed to have a similar ability to relieve the positive symptoms of schizophrenia, such as disturbing symptoms like hallucinations and delusions, by helping to block the excess dopamine.

Doctors will usually prescribe typical antipsychotic medication, such as Chlorpromazine or Haloperidol, following the first psychotic episode of Schizophrenia.  There are many typical drugs available: Chlorpromazine (Thorazine), Fluphenazine (Prolixin), Haloperidol (Haldol), Thiothixene (Navane), Trifluoperazine (Stelazine), Perphenazine (Trilafon), and Thioridazine (Mellaril).

Not all the above drugs are phenothiazines, but they do work in similar ways. The above drugs are, however, all typical antipsychotics, i.e., they all work on blocking dopamine receptors.

A03 ANALYSIS OF TYPICAL ANTIPSYCHOTICS

A major disadvantage of typical antipsychotics is that about thirty per cent of patients with Schizophrenia do not respond to the drugs, although some of these patients may respond better to the newer atypical antipsychotics (see the section on a-typical drugs).

This percentage may reflect the fact that not all patients with schizophrenia have positive symptoms, indeed many present only with negative symptoms. Typical antipsychotics do not help with negative symptoms, such as avolition, anhedonia and poverty of speech. In fact, this first group of antipsychotics often made negative symptoms worse.

This finding was a major disadvantage for not only the success rate of typical antipsychotics but also the original dopamine hypothesis as it meant that the hyper dopamine hypothesis of schizophrenia could only be partially correct at most.

Of course, it is now acknowledged in the dopamine 2 hypothesis that some schizophrenics have hypo dopamine production in certain areas of the brain, which makes sense as negative symptoms predominantly have to do with a lack of pleasure and movement, which in turn are strongly correlated with low levels of Dopamine. It seems reasonable, therefore, that giving patients who present with negative symptoms dopamine antagonists such as typical antipsychotics will cause their dopamine production to further deplete, which would then exacerbate negative symptoms.

Another major drawback of typical anti psychotics is there drop out rate, Half the patients who take antipsychotics quit after one year and up to three-quarters of patients quit before two years. Questionnaire surveys reveal that many schizophrenics drop out of typical drug treatments because of the hideous side effects, especially Tardive Dyskinesia (Lieberman et al, 2005). Tardive Dyskinesia is a neurological condition characterised by repetitive, involuntary, purposeless movements, such as grimacing, tongue protrusion, lip-smacking, puckering and pursing of the lips, and rapid eye blinking. This syndrome affects about 10 – 20 per cent of patients treated with typical antipsychotics. The longer patients are prescribed typical antipsychotics, the higher the chance they will not only develop Tardive Dyskinesia but also that the condition will become permanent. Some schizophrenic patients have described tardive dyskinesia as more distressing than schizophrenia.

As a result of side effects, patients often stop taking medications when symptoms get better and end up relapsing. In mental health, revolving door syndrome refers to the tendency of clients to get better for a while, and then end up relapsing. It most often applies to those with serious disorders, such as schizophrenia, but anyone with a mental health condition could potentially be at risk.

Because of such serious side effects, some clinicians believe it is unwise to prescribe high doses of typical antipsychotics for extended periods. Many Schizophrenics are given very small doses of the drug. Obviously, this presents the clinician in a bind, if medication is reduced, the chance of relapse increases; but if medication increases; serious and untreatable side effects may develop.

ATYPICAL DRUGS 1990S

Atypical drugs block dopamine and serotonin.

• In the last decade, new "atypical" antipsychotics have been introduced. Atypical antipsychotics work differently from typical antipsychotics. Although it is not acknowledged precisely how they work, it is known they have a major impact on serotonin receptors. Compared to the older "conventional" antipsychotics, these medications have been heralded as not only equally effective at reducing positive symptoms like hallucinations and delusions - but also better at relieving the negative symptoms such as withdrawal, poor thinking skills, and lack of energy. 

• Atypicals act on both dopamine and serotonin receptors

• Atypicals work for individuals who do not respond to typical antipsychotics..

• Pharmaceutical companies say there are fewer side effects; therefore, patients are more likely to continue taking the drug and see the benefits. Treatment guidelines recommend using one of the atypical antipsychotics other than clozapine as a first-line treatment option for newly diagnosed patients. However, for people already taking a conventional antipsychotic medication that is working well, a change to an atypical may not be the best option.

• Atypical antipsychotics include Risperidone (Risperdal), Clozapine (Clozaril), Olanzapine (Zyprexa), Quetiapine (Seroquel), and Ziprasidone (Geodon).

• Clozapine was the first atypical antipsychotic in the United States and seems to be one of the most effective medications, particularly for people who have not responded well to other medications. Treatment-resistant schizophrenia" is a term used for the failure of symptoms to respond satisfactorily to at least two different antipsychotics.

  A03: However, in some people, Clozapine has a serious side effect of dramatically lowering the number of white blood cells produced (Agranulocytosis). As a result, it can impair the functioning of the immune system and make people vulnerable to serious infection and even death. This condition affects 1 per cent of people who take it. Patients taking Clozapine must monitor their blood every one or two weeks to count the number of white blood cells in the bloodstream. For this reason, Clozapine is usually the last atypical antipsychotic prescribed and is usually used as a last-line treatment for people who do not respond well to other medications or have frequent relapses.

  For other patients who are unwilling or unable to take medication regularly, long-acting depot preparations of antipsychotics may be given every two weeks to achieve control.

EVALUATION ATYPICAL ANTIPSYCHOTICS

Atypical antipsychotics may be less likely to cause Tardive dyskinesia, but there are many new side effects.

• Massive weight gain of up to a stone per year. This does not even out, weight gain is consistent whilst taking atypicals. As a result, diabetes is also a very common side effect for patients taking these types of drugs.

• Agranulocytosis.

• Extrapyramidal side effects stem from a dysfunction of the nerve tracts that descend from the brain to spinal motor neurons. Extrapyramidal side effects resemble the symptoms of Parkinson’s disease such as Tremors of the fingers, a shuffling gait and drooling.

• Dystonia, a state of muscle rigidity and dyskinesia, and an abnormal motion of voluntary and involuntary muscles producing chewing movements as well as other movements of the lips, fingers and legs; together, they cause arching of the back and a twisted posture of the neck and body.

• Akathesia is an inability to remain still; people pace constantly and fidget. People with akathisia have a desire to keep moving. They are unable to keep still even though their movements are voluntary (as opposed to other movement disorders such as tardive dyskinesia which is involuntary). It most often affects the legs. When mild it is usually worse at night. These perturbing symptoms can be treated with drugs used with patients who have Parkinson’s disease.

• Tardive Dyskinesia, A muscular disturbance, e.g., mouth muscles involuntarily make sucking lip-smacking and chin-wagging motions. In more severe cases the whole body can be subject to involuntary motor movements. Although tardive dyskinesia is less common with atypicals (5% of those on atypical versus 20-30% on typical), For example, Jeste et al.: after nine months, 30% of patients using conventional drugs developed the disease: 5% using atypical. Tardive Dyskinesia is not responsive to any known treatment (although clinicians do try and use Botox to paralyse the facial muscles and or combine agonists with antagonists to lessen the condition).

• Neuroleptic malignant syndrome occurs in about 1% of cases. In this condition which can sometimes be fatal, severe muscle rigidity occurs accompanied by fever. The heart races, blood pressure increases and the patient may lapse into a coma.

• All the other side effects common with typical

Common side effects of all antipsychotics include:

• Dizziness,

• Blurred vision

• Restlessness

• Sexual dysfunction

• America and Australia are two countries with laws allowing the forced administration of anti-psychotics on those who refuse but are otherwise stable and living in the community. As side effects are so serious, forcing these drugs on people against their will is extremely unethical.

A03 EVALUATION OF ANTIPSYCHOTICS: TYPICAL AND ATYPICAL

Before Antipsychotic drugs, 50% of patients admitted to the hospital stayed there for life. The treatment of inmates in lunatic asylums was brutal or non-existent. For example, electric compulsive therapy, frontal lobe lobotomy, insulin shock therapy etc. Moreover, the living conditions were disgraceful and inhumane. Hospital staff mainly used methods to control, contain and restrain patients, not treat them: straitjackets and padded cells. In comparison, today only 3% of Schizophrenics are in hospital and usually only for a few weeks. Therefore, the treatment of the mentally ill in Western/individualistic societies has changed radically for the better. However, it is likely that with the level of social awareness that is now prevalent in Western societies, patients with mental health problems would not be treated so inhumanely today, even without drug treatments being an option. Drugs did not cause greater humanity they just pushed the problem away from poorly educated staff and practitioners.

Atypical and typical antipsychotic drugs supposedly decrease most positive and negative symptoms. As a result, the lives of schizophrenic patients have become revolutionised, e.g., being able to cope better with their lives, jobs and relationships.

It is disputed how much antipsychotics enable patients to live normal lives as research on the effectiveness of typical and atypical antipsychotics is very mixed. For example:

Davis et al: when reviewing the relapse rate of 29 studies it was found that there was a higher relapse rate using the placebo (55%): and drug (19%) Ross et al: said this study is misleading as it doesn’t take into account that 45% of people did benefit from the placebo.

Davis et al also showed that when comparing two environments ( hostile or supportive ) with two conditions (drugs or placebo). The result shows that drugs work better when combined with family therapies such as expressed emotion, but there is little difference in supportive environments.

Patients living in hostile and critical environments,

• The relapse rate using drugs was 53%

• The relapse rate using a placebo was 92% with a placebo.

  Patients living in a supportive environment

• The relapse rate using drugs was 12%:

• The relapse rate using a placebo was 15%

Leutch et al: two out of four atypical drugs were more effective compared to conventional – the other two other drugs showed no difference

• A comprehensive randomised clinical trial compared four atypical drugs and one typical drug against one another (Lieberman et al, 2005). Close to 1,500 patients from all over the USA took part. Among the many findings of this study, three things stood out.  First, the atypical drugs were not more effective than the typical drugs despite the publicity saying they were. Secondly, the atypical drugs did not produce fewer side effects than typical antipsychotics.

• Lastly, nearly three-quarters of patients had stopped taking the drugs before the 18 months of the study design had ended.

• 50% of patients stop taking their medication after the first year

  75% of patients stop taking their medication by the second year.

  Of those still taking drugs, 40% relapse in the first year and 15% each subsequent year. These figures imply that antipsychotics are not very effective as most patients discontinue treatment (because of medication side effects, disorganized thinking, or because they feel the medication is no longer working).  Plus a significant amount of patients are not symptom-free.

  Ross et al.: drugs reduce the effects but not the cause, and therefore they decrease the motivation of the patient to find the cause of schizophrenia.

OTHER A03

Drug treatments need to be started quickly to be most effective, and those patients who remain untreated for many years often do not benefit when treatments are finally started. Some patients do not respond to any antipsychotic at all.

• Upregulation = Increased exposure to an antagonist drug can increase the number of receptors (upregulation).

• Down-regulation = Increased exposure to an agonist drug can result in a decrease in the number of receptors (downregulation).

There is a risk that giving patients antipsychotics is akin to putting them into a “pharmacological straitjacket”-as some questionnaires reveal that medications can make patients feel zombied ‘and out of touch with their feelings. Critics of psychiatry suggest that psychotropic drugs are prescribed for the benefit of the family, hospitals and society. There is some evidence that all psychotropic drugs, pharmaceutical and illegal, cause brain chemistry regulation, formally known as down-regulation and up-regulation of a neurotransmitter. For example, if patients are taking agonists such as SSRIs, then they will experience down-regulation in their own serotonin systems, And if a patient is taking antagonists such as antipsychotics, then they will experience up-regulation of their dopamine systems.

Upregulation and downregulation are the brain’s chemical responses to drugs. Thus, if a person takes antagonists, which decrease the availability of dopamine, then the brain compensates for the reduction in dopamine availability by increasing dopamine levels naturally. Likewise, people who take agonists, which increase the availability of a neurotransmitter like serotonin, have a brain response that decreases the availability of serotonin. This is known as downregulation. This essentially means that people on antipsychotics will eventually have more dopamine availability to compensate for the loss, thereby making the person more prone to psychosis, and people on antidepressants will become more depressed.

“Current antipsychotic drugs are not treating the primary abnormality and are acting downstream. While antipsychotic drugs block the effect of inappropriate dopamine release, they may paradoxically worsen the primary abnormality by blocking presynaptic D2 autoreceptors, resulting in a compensatory increase in dopamine synthesis. There is some evidence from healthy volunteers that acute antipsychotic treatment does increase presynaptic dopamine synthesis capacity, one and while successful subacute treatment can reduce this, it is nevertheless elevated in patients who have received antipsychotic treatment for many years. This may explain why patients relapse rapidly on stopping their medication, and if the drugs may even worsen the primary abnormality, it also accounts for more severe relapse after discontinuing treatment. This suggests that drug development needs to focus on modulating presynaptic striatal dopamine function, either directly or through upstream effects withdrawal – sometimes coming off the drug produces symptoms far worse than the original ones.”

ALTERNATIVE TREATMENTS

Some findings indicate that drugs may not even be necessary. In the long term, many schizophrenic individuals function better without antipsychotic medicine so perhaps this indicates nurture may be more important.. In a 2007 study, only 28% of patients who were not being treated medicinally showed signs of psychotic activity, while 64% of those on antipsychotics had psychotic activity. Furthermore, people who suffer from schizophrenia in the Third World are twice as likely to recover as sufferers in the West, according to a report by the World Health Organisation (WHO). The World Health Organisation conducted two long-term follow-up studies involving more than 2,000 people suffering from schizophrenia in different countries. These studies found patients have much better long-term outcomes in developing countries (India, Colombia and Nigeria) than in developed countries (USA, UK, Ireland, Denmark, Czech Republic, Slovakia, Japan, and Russia), despite the fact antipsychotic drugs are typically not widely available in poorer countries, raising questions about the effectiveness of such drug-based treatments. Professor Leff of the Institute of Psychiatry in London said the outcome was better in non-western countries because of strong support networks, the opportunity to work and the lack of stigma in areas where beliefs in witchcraft and karma mean the condition is accepted more easily.

"A large number of people in households [in developing countries] means that there is a network of people who can share the responsibility for the patient's care and recovery. There is a strong sense of duty, and they all share the burden. In the West, you are more likely to find a middle-aged person with schizophrenia being cared for by one carer and the burden of emotional and physical care falls on one person."

Determinism? See other discussions and adapt. You can’t help yourself you must rely on drugs. No free will. Parents can do nothing. This contradicts evidence from cross-cultural studies and patients receiving CBT/EE training and those receiving no meds.

Ethics?  E.g.  Informed consent can the mentally ill give informed consent? Horrendous side effects.  Death. Should you give placebos to Schizophrenics? How can it be avoided? 

Reductionism? Reducing treatment to blocking Dopamine suggests that the cause and treatment are biological only. Research shows it is not just biological. Eclectic approaches are thought to be more effective. For example, in one study, patients were randomly assigned to drug treatment or a new treatment involving the following components:

• Educating patients about relapse and getting them to spot early signs

• Staff monitoring early signs of relapse

• Weekly support group and/or individual therapy

• Family education sessions

• Quick drug interventions

After 18 months, results showed that the new treatment cut hospitalisation and relapse by 44%.

IS PSYCHOLOGY A SCIENCE?

See the above table of A01 research. Is the research scientific experimental, or are the quasi/natural experiments? Most studies on relapse have been highly scientific and well-designed. Review individual studies yourselves.

However, there are ethical issues when researching drug treatments. Ideally, you would compare patients who are on different drugs and placebo. However, it is difficult to control extraneous variables if you do this. You should not give placebos and randomly allocate schizophrenics to different drug groups, as it is unethical when someone is that seriously ill and may be very depressed.

Schizophrenia as a diagnosis pulls together a group of people who vary considerably in symptom presentation and course, number of hospital admissions, self-esteem, depression, suicidality, social/family support, response to medication, etc., this makes the research less valid and reliable. Again, if the classification of schizophrenia is invalid (think of our previous discussion here), then how can treatments be effective? If you assess schizophrenia incorrectly, then your patients may not have it; hence treatments will not reflect real Schizophrenia.

NATURE VERSUS NURTURE

If the cause is not one thing, e.g. neither just nature (biological) nor nurture (psychological: cognitive, psycho-dynamic, Behavioural, etc.), then should treatment reflect this? E.g. treatment should be both biological (drugs) and psychological (counseling). See the above study on reductionism to support this and stress diathesis model.