Formal Thought Disorder

Just like when a physician sees a patient and looks for signs of physical illness, when a psychiatrist meets a patient they are looking for signs of psychiatric illness.  This is important because when people are suffering a deterioration in their mental health, they often describe similar experiences and these signs of mental illness are referred to as psychopathology.  When different psychopathological signs are identified and grouped together they can lead to the formation of a psychiatric diagnosis.

One of the most interesting psychopathology signs is formal thought disorder (FTD) which refers to the sort of disorganised speech which is a manifestation of psychosis. 

When people are describing a patient’s mental state they often write ‘no FTD’ when they wish to convey that the patient is coherent and can make themselves understood.  It’s a little bit more subtle than that; if a patient is intoxicated or delirious they will be incoherent but they will not necessarily be thought disordered.  Thought disorder refers to a particular set of language errors which are seen in psychosis. 

The name is rather strange.  Although it is called ‘formal thought disorder’ it actually refers to what a patient is saying.  The name is historical as when disorders of speech due to psychiatric illness were first being described (Bleuler, amongst others, was important in this), it was felt that disorders of thought form (disorganised speech) and content (delusions) should be considered separately.  Formal thought disorder therefore is a disorder of speech rather than content*.  

Normal human thinking has three characteristics

1. Content: what is being thought about – this would include delusions and obsessional thoughts

2. Form: in what manner, or shape, is the the thought about; abnormalities of the way thoughts are linked together

3. Stream or flow: how it is being thought about – the amount and speed of thinking

Different elements of formal thought disorder have been described. With his early work, Bleuler considered FTD to be when there was a loosening of associations which lead to fragmentary ideas being connected illogically.  This is seen clearly in the picture above.  Confusingly though, there appears to be no consensus about exactly what can be included formal thought disorder; it appears that most people would now use the term ‘thought disorder’ which refers to both errors of form and stream. Content is still considered separately.  

Disorder of stream of thought 

(I’ve split up these into disorder of thought form and stream, but several could be argued both ways) 

Flight of ideas is when the content of speech moves quickly from one idea to another so that one train of thought is not carried to completion before another takes its place.  The normal logical sequence of ideas is generally preserved although ideas may be linked by distracting cues in the surroundings and from distractions from the words that have been spoken.  These verbal distractions may be of three kinds: clang associations, puns and rhymes.

Retardation of thinking is often seen in depression, the train of thought is slowed down, although still goal directed.  The opposite is pressure of speech and this is often seen in mania.

Peseveration is the persistent and inappropriate repetition of the same thoughts.  In reply to a question a person may give the correct answer to the first but continue to give the same answer inappropriately to subsequent questions.  This is especially seen in ‘organic’ brain disorders like dementia.

Disorders of thought form:

Overinclusion refers to a widening of the boundaries of concepts such that things are grouped together that are not often closely connected. 

Loosening of associations denotes a loss of the normal structure of thinking.  The patient’s discourse seems muddled and illogical and does not become clearer with further questioning; there is a lack of general clarity, and the interviewer has the experience that the more he/she tries to clarify the patient’s thinking the less it is understood.  Loosening of associations occurs mostly in schizophrenia

Three kinds of loosening of association have been described:

Knight’s move thinking or derailment where there are odd tangential associations between ideas. 

Talking past the point (= vorbeireden) where the patient seems to get close to the point of discussion, but skirts around it and never actually reaches it

Verbigeration (= word salad = schizophasia =paraphrasia) where speech is reduced to a senseless repetition of sounds and phrases  (this is more of a disorder of thought form)

Circumstantiality is where thinking proceeds slowly with many unnecessary details and digressions, before returning to the point.  This is seen in epilepsy, learning difficulties and obsessional personalities 

Neologisms are words and phrases invented by the patient or a new meaning to a known word

Metonyms are word approximations e.g. paperskate for pen

Derailment (aka entgleisen) is where there is a change in the track of thoughts.  There is perserved, but misdirected determining of tendency/goal of thought)

With drivelling there is a disordered intermixture of the constituent parts of one complex thought

Fusion is where various thoughts are fused together, leading to a loss of goal direction.

Omission is where a thought or part of a thought it is senselessly omitted

Substitution is where one thought fills the gap for another appropriate more ‘fitting-in’ thought.

Concrete thinking is seen as a literalness of expression and understanding, with failed abstraction.  Can be tested by the use of proverbs.

Thought block  refers to the sudden arrest in the flow of thoughts.  The previous idea may then be taken up again or replaced by another thought.

As you can tell this is a big subject and I haven’t got onto the historical attempts to characterize schizophrenic thought processes (by Kraepelin, Bleuler, Goldstein, Cameron andSchneider) or the linguistic classification of speech abnormalities in psychosis. 

Further reading

Andreasen NC. Thought, language, and communication disorders. I. A Clinical assessment, definition of terms, and evaluation of their reliability. Archives of General Psychiatry 1979;36(12):1315-21

*Quite why they choose this name though it unclear to me, and if anyone else can shed more light on it I would be grateful. 

Long Acting Injectable Antipsychotics: A Primer

By KELLY GABLE, PHARMD, BCPP & DANIEL CARLAT, MD

They used to be called “depot” antipsychotics, but the powers that be have renamed them “long acting injectables” (LAIs), presumably to help remove some of the stigma associated with their use. But no matter what you call them, suddenly every drug company is racing to introduce its own LAI neuroleptic. In 2009 Janssen introduced Invega Sustenna (paliperidone palmitate)—its possibly beacause older LAI, Risperdal Consta, will go off patent soon—and shortly thereafter Eli Lilly unveiled the LAI version of olanzapine, Zyprexa Relprevv. Over the next few years, we should expect to see LAI formulations of both aripiprazole (Abilify) and iloperidone (Fanapt).
Are these new formulations really any better than those old workhorses, haloperidol (Haldol Decanoate) and fluphenazine (Prolixin Decanoate)? In this review we will look at how the newer atypical LAIs compare with the conventionals, we will give you some practical tips for how to dose these agents.
Do depot meds really improve adherence?
It’s no secret that our patients with schizophrenia often stop taking their medications; in fact, about 75% of these patients will discontinue their antipsychotic therapy within two years of hospital discharge (Weiden PJ and Zygmunt A, J Prac Psych Behav Health1997;3:106–110). The obvious selling point of LAIs is that they might improve patient adherence, since the injections need be given only every two to four weeks, depending on the medication. But have any head-to-head studies actually demonstrated an adherence advantage of LAIs?
Surprisingly, the answer appears to be: “not really.” A 2005 Cochrane review, for example, looked at six randomized controlled studies (comprising 419 patients) comparing injectable fluphenazine with oral antipsychotics, and found that the depot medication did not reduce relapse more than oral neuroleptics (David A et al, Depot fluphenazine decanoate and enanthate for schizophrenia. Cochrane Database Syst Rev 2005, Issue 1).
A more recent study focused specifically on injectable risperidone (Risperdal Consta), finding the same lackluster performance. These researchers examined medication records of 11,821 VA patients with schizophrenia. Of the patients prescribed injectable risperidone, only 44.6% continued treatment for 18 months or longer, significantly fewer than those on oral agents such as clozapine (Clozaril) (77.1%) or other oral antipsychotics (57.9%) (Mohamed S et al, Psychiatr Q2009;80(4):241–249).

This article originally appeared in The Carlat Psychiatry Report -- an unbiased monthly covering all things psychiatry.
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Finally, yet another study, this one of a large Medicaid sample, found that fewer than 10% of patients who started on LAIs in the hospital were still on them at six months post-discharge (Olfson M et al,Schizophr Bull 2007;33(6):1379–1387).
Which depot med should you choose?
Though the research has not shown an adherence advantage for LAIs in the large populations studied, there are clearly some individual patients who will benefit from depot formulations. In such patients, which medication should you choose, and how should you dose it?
The first decision point is whether to prescribe a conventional or an atypical LAI. There have been no published trials comparing the two, so we have no real evidence base to guide us. In head to head trials of oral meds, however, atypicals have in general been no more effective than typicals, though the side effect profiles differ. High potency typicals cause more extrapyramidal symptoms (EPS) and tardive dyskinesia, while some of the atypicals—especially olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal)—cause more obesity and higher diabetes risk (Lieberman JA et al, NEJM2005;353(12):1209–1223). Moderate potency conventionals, such as perphenazine (Trilafon) are potentially good choices, since they cause few EPS and little weight gain. Unfortunately, there is no depot version of perphenazine.
The two available conventional LAIs—haloperidol and fluphenazine—are high potency neuroleptics, and the primary advantage of both of them is cost. A monthly dose of 200 mg of haloperidol decanoate is around $15, versus $900 a month for Risperdal Consta 37.5 mg, or $1,185 a month for a 156 mg dose of Invega Sustenna (price data from Morris & Dickson, wholesale pharmaceutical distributor).
Thus, you can save the health care system a chunk of change by choosing haloperidol and using an anticholinergic to prevent EPS—about $12,000 per year, money that might be better spent for a good case worker, for example. Aside from cost issues, you might choose a conventional agent for patients who have responded well to either haloperidol or fluphenazine in the past with few side effects.
Among the atypical LAIs, we currently have three agents to choose from: Risperdal Consta, Invega Sustenna, and Zyprexa Relprevv. There are subtle differences among all the LAIs, and in order to understand how to make an informed decision, you need to know a bit of the nuts and bolts of how they are packaged.

Injection Packaging and Delivery System Differences

Typical antipsychotic LAIs
Because both haloperidol and fluphenazine are dissolved in oil, they are the most painful to inject. Once administered, fluphenazine peaks quickly, within eight to 10 hours after injection, so an oral fluphenazine overlap may not be necessary, though some clinicians choose to give oral fluphenazine for a few days just to play it safe.
The plasma concentration of haloperidol, on the other hand, rises gradually and peaks at about six days after the first injection. Strictly speaking, therefore, an oral overlap of about a week is necessary, though standard clinical practice is to continue oral haloperidol for two to three weeks to prevent symptom relapse.
Another major difference between the two agents is ease in dosing. Haloperidol is often preferred due to the simple oral to intramuscular conversion: 10 to 15 times the oral dose will provide you with a decent monthly injection dose (McEvoy JP, J Clin Psychiatry2006;67(suppl 5); Haloperidol Decanoate [package insert]. Titusville, NJ: Ortho-McNeil Neurologics; 2004). The fluphenazine conversion is 1.2 times the oral dose, making the mathematics somewhat more complicated (Fluphenazine [package insert]. Richmond Hills, ONT: Novex Pharma; 2001).
Atypical antipsychotic LAIs
Risperdal Consta differs from the other injectables in that it comes as a powder that must be refrigerated. Just prior to injection, you have to mix the powder in saline and shake it up. While none of this is a real deal breaker, the administration process is more involved than its counterparts. Because the drug is in saline, the injection is not too painful, and after the initial injection, only 1% of the drug is released immediately. It is not until week three that the tiny microspheres release the drug slowly into the body, meaning that a three week oral overlap is necessary to prevent the patient from becoming symptomatic. Aside from the burden of an oral overlap, Risperdal Consta is rather easy to dose if you follow the general rule that 25 mg intramuscular is roughly equal to 2 to 4 mg oral (Risperdal Consta [package insert]. Titusville, NJ: Jansson; 2007; Kane JM, J Clin Psychiatry 2003;64(suppl 16)).
If your patient refuses or is unable to take oral medication, Invega Sustenna and Zyprexa Relprevv are potential alternatives (as is fluphenazine). Both Invega Sustenna and Zyprexa Relprevv begin acting right away, so no oral overlap is needed. Both medications are also conveniently packaged as pre-filled syringes; however, dosing can be a bit tricky. For example, Invega Sustenna requires two separate loading doses one week apart (234 mg on day one, and 156 mg on day eight). The maintenance dose, usually 117 mg (the equivalent of 6 mg oral), is given every four weeks (Bishara D,Neuropsychiatr Dis Treat 2010;6(1):561–572).
We’ll get to Zyprexa Relprevv soon, but first, how do you choose between Risperdal Consta and Invega Sustenna? If you read our issue lambasting oral paliperidone (Invega)(TCPR, March 2007), you already know that it is simply 9-hydroxyrisperidone, ie, the active metabolite of risperidone.
Both Invega and Invega Sustenna are “me-too” drugs, and their only advantages over risperidone are that they are less prone to drug-drug interactions, and may be safer for patients with liver impairment. However, there have been no head-to-head trials comparing Risperdal Consta and Invega Sustenna, and we shouldn’t expect to see them anytime soon.
There are some practical differences between the two agents that psychiatrists should be aware of: 1) Risperdal Consta is administered every two weeks versus every four weeks with Invega Sustenna; 2) Consta requires a three week oral overlap, Sustenna does not; and 3) Sustenna is slightly more expensive than Consta, depending on your maintenance dose. It costs around $3,000 to initiate the two loading doses for Sustenna, but the eventual monthly maintenance cost is about $1,000, only a little more than Consta.
That leaves us with the last atypical antipsychotic LAI to reach the market, Zyprexa Relprevv. Clinical trials for Relprevv began in 2000 but it was not approved by the FDA until 2009. This delay was due to a potentially serious side effect—post-injection delirium/sedation syndrome. During clinical trials there were 30 reported cases of accidental intravascular injection of a portion of the medication, which clinically presents like an olanzapine overdose.
The side effect is rare, occurring in about 0.07% of injections (Citrome L, Int J Clin Pract 2009;63(1):140–150). The time to onset of these symptoms is anywhere from zero to 300 minutes. For this reason, the patient must be observed for three hours post-injection by a healthcare professional (Lorenzo RD and Brogli A, Neuropsychiatr Dis Treat 2010;6(1):573–581).
In order to prescribe Zyprexa Relprevv, you must register with Eli Lilly’s Patient Care Program, a seemingly tedious proposition akin to the nationwide clozapine registry. Not only do you have to register as a prescriber, but the healthcare facility and pharmacy provider must also register to dispense the product.
The bottom line on LAIs is that their putative benefits in terms of getting patients to stay on meds have yet to be proven. While it’s true that the injection keeps the bloodstream rich in neuroleptic for two to four weeks, many patients just hate getting the injections and eventually stop submitting to them. They are best used for select patients who are clearly on board with the program.
In terms of which LAIs to choose, Haldol Decanoate is so much less expensive than the atypicals that you really have to think twice before prescribing one of the newer agents. If you do go with an atypical LAI, we recommend that you avoid Zyprexa Relprevv if humanly possible, and that you choose Risperdal Consta over Invega Sustenna.

Why Consta over Sustenna? As it goes generic it will become much less expensive, and the need for every two week injections is paradoxically a benefit for many patients, since it forces them to show up at the clinic more frequently, allowing us to monitor their symptoms more closely.
TCPR VERDICT: Use ultra-cheap Haldol Decanoate in those who can tolerate it, choose Risperdal Consta over Invega Sustenna, and avoid Zyprexa Relprevv completely.

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Xeplion (paliperidone)

4

Main use	Active ingredient	Manufacturer
Schizophrenia	Paliperidone palmitate	Janssen-Cilag

How does it work?

Xeplion injections contain the active ingredient paliperidone, which is a type of medicine called an atypical antipsychotic.

Paliperidone works in the brain, where it affects various neurotransmitters, in particular dopamine and serotonin (5HT). Neurotransmitters are chemicals that are stored in nerve cells and are involved in transmitting messages between the nerve cells.

Dopamine and serotonin are neurotransmitters known to be involved in regulating mood and behaviour, amongst other things. Psychotic illness is considered to be caused by disturbances in the activity of neurotransmitters (mainly dopamine) in the brain. Schizophrenia is known to be associated with an overactivity of dopamine in the brain, and this may be associated with the delusions and hallucinations that are a feature of this disease.

Paliperidone works by blocking the receptors in the brain that dopamine acts on. This prevents the excessive activity of dopamine and helps to control schizophrenia.

People with schizophrenia may experience 'positive symptoms' (such as hallucinations, disturbances of thought, hostility) and/or 'negative symptoms' (such as lack of emotion and social withdrawal). Paliperidone is effective in relieving both positive and negative symptoms of schizophrenia, whereas older antipsychotics are usually less effective against the negative symptoms.

Paliperidone also relieves 'affective symptoms' that are associated with schizophrenia, such as depression, guilt feelings or anxiety.

Xeplion injection is a type of injection called a depot injection. It is administered into the muscle of the upper arm or buttock, where it forms a reservoir of medicine that is slowly released into the bloodstream. The injection is given once every four weeks.

What is it used for?

• Schizophrenia (in people who have previously responded to paliperidone or risperidone treatment taken by mouth).

How is this treatment given?

• This medicine is for injection into a muscle only. It must not be administered under the skin or into a vein. You will be given the injection by a medical professional who has been appropriately trained in the technique.
• Xeplion injection is administered into the muscle of either the buttock or the upper arm, where it forms a reservoir of medicine that is slowly released into the bloodstream.
• The first two doses of the injection are given into the upper arm, one week apart, to allow for the concentration of the medicine to build up rapidly in the body. After that, Xeplion is given once a month into either the upper arm or buttock. The injection site should be alternated between the left and right sides of the body. It is a good idea to make a note of the date when your injection is administrated and when your next injection is due. (Your monthly injection can be given a week early or a week late if necessary.)
• Unless your doctor tells you otherwise, you should not suddenly stop treatment with this medicine, even if you feel better and think you don't need it any more. This is because the medicine controls the symptoms of the illness but doesn't actually cure it. This means that if you suddenly stop having the injections your symptoms could come back. When treatment with this medicine is stopped, it should be done gradually, following the instructions given by your doctor.

Warning!

• This medicine may cause drowsiness or dizziness. If affected do not drive or operate machinery. You should avoid drinking alcohol because it is likely to make any drowsiness or dizziness worse.
• This medicine can occasionally cause your blood pressure to drop when you move from a lying down or sitting position to sitting or standing, especially when you first start treatment with the medicine. This may make you feel dizzy or unsteady. To avoid this try getting up slowly. If you do feel dizzy, sit or lie down until the symptoms pass.
• This medicine can cause some people to put on weight and your doctor will want to weigh you regularly. Talk to your doctor about this before you start treatment so that you can discuss strategies, such as diet and exercise, for minimising any weight gain.
• Antipsychotic medicines can sometimes affect the ability of the body to control its core body temperature. This is more likely to be a problem in elderly people and can result in heat stroke in hot temperatures and hypothermia in cold temperatures. It is important to avoid situations that can result in you overheating or getting dehydrated. Ask your doctor or pharmacist for more advice.
• This medicine may rarely cause a decrease in the normal amounts of blood cells in the blood. For this reason you should consult your doctor immediately if you experience any of the following symptoms: unexplained bruising or bleeding, purple spots, sore throat, mouth ulcers, high temperature (fever), feeling tired or general illness. Your doctor may want to take a blood test to check your blood cells.
• Antipsychotic medicines are associated with an increased risk of getting a blood clot in a vein (deep vein thrombosis) or in the lungs (pulmonary embolism). For this reason, you should consult a doctor immediately if you get any of the following symptoms, which could suggest you have a blood clot: stabbing pains and/or unusual redness or swelling in one leg, pain on breathing or coughing, coughing up blood or sudden breathlessness.
• Consult your doctor immediately if you experience any abnormal movements, particularly of the face, lips, jaw and tongue, while you are on this medicine. These symptoms may be indicative of a rare side effect known as tardive dyskinesia, and your doctor may ask you to stop treatment with this medicine, or decrease your dose.
• Consult your doctor immediately if you experience the following symptoms while having Xeplion injections: high fever, sweating, muscle stiffness, faster breathing and drowsiness or sleepiness. These symptoms may be due to a rare side effect known as the neuroleptic malignant syndrome, and your treatment may need to be stopped.

Use with caution in

• Elderly people.
• Severely decreased liver function.
• Decreased kidney function.
• Diabetes (if you have diabetes your blood sugar levels should be monitored closely while you are having treatment with this medicine, because it may increase your blood sugar).
• People with disease involving the heart and blood vessels (cardiovascular disease) for example heart failure, angina, previous heart attack or an irregular heartbeat (arrhythmia).
• People with a personal or family history of an abnormal heart rhythm seen as a 'prolonged QT interval' on a heart monitoring trace or ECG.
• People with low blood pressure (hypotension).
• People who are dehydrated.
• People with a history or risk of stroke or small temporary strokes (transient ischaemic attacks).
• Elderly people with dementia and a risk of stroke (other similar antipsychotic medicines are associated with an increased risk of stroke and death in this group of people).
• People with a personal or family history of blood clots (venous thromboembolism), for example in a vein of the leg (deep vein thrombosis) or in the lungs (pulmonary embolism).
• People with other risk factors for getting a blood clot, for example smoking, being overweight, taking the contraceptive pill, being over 40, recent major surgery or being immobile for prolonged periods.
• People with a history of seizures, eg epilepsy.
• People with conditions that increase the risk of epilepsy or convulsions, eg brain damage or withdrawal from alcohol.
• Parkinson's disease.
• People with a history of a drop in the numbers of white blood cells in the blood, particularly if this was caused by a medicine.
• People with a tumour of the pituitary gland in the brain that produces the hormone prolactin (prolactinoma).
• People with tumours whose growth may be stimulated by the hormone prolactin, eg breast cancer.

Not to be used in

• People who are allergic to risperidone.
• Breastfeeding.
• This medicine is not recommended for people with moderate to severely decreased kidney function.
• This medicine is not recommended for children less than 18 years of age, as its safety and efficacy have not been established in this age group.
• Xeplion injection does not work quickly enough to manage people who are acutely agitated or in a severely psychotic state and who need a treatment that immediately controls their symptoms.

This medicine should not be used if you are allergic to any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy. If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

• The safety of this medicine for use during pregnancy has not been established. It should not be used during pregnancy unless considered essential by your doctor, and only if the potential benefits to the mother outweigh any possible risks to the unborn child. Antipsychotics used during the third trimester could cause side effects or withdrawal symptoms in the baby after birth and the baby may need extra monitoring because of this. Seek further medical advice from your doctor.
• If you do get pregnant while having treatment with this medicine it is important to consult your doctor straight away for advice. You should not suddenly stop treatment with this medicine unless your doctor tells you to, as this could cause your symptoms to come back.
• This medicine passes into breast milk and could be harmful to a nursing infant. It should not be used during breastfeeding. Mothers who need treatment with this medicine should not breastfeed. Seek further medical advice from your doctor.

Label warnings

• This medication may cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

Very common (affect more than 1 in 10 people)

• Difficulty sleeping (insomnia).
• Headache.

Common (affect between 1 in 10 and 1 in 100 people)

• Dizziness.
• Sleepiness (somnolence).
• Depression.
• Anxiety, restlessness and agitation (akathisia).
• Abnormal movements of the hands, legs, face, neck and tongue, eg tremor, twitching, rigidity (extrapyramidal effects).
• Faster or slower than normal heartbeat.
• Cough.
• Blocked nose.
• Disturbances of the gut such as nausea, vomiting, abdominal pain or discomfort, indigestion, diarrhoea or constipation.
• Fatigue, weakness or loss of strength (asthenia).
• Reaction at site of injection.
• Infection of the upper respiratory tract.
• High blood pressure.
• Back pain.
• Increased blood glucose levels. Tell your doctor if you notice you feel unusually hungry or thirsty, or need to pass urine more often than usual. People with diabetes should monitor their blood sugar closely.
• Increased weight. Your doctor will want to weigh you regularly to make sure you are not gaining too much weight.
• Elevated levels of fats called triglycerides in the blood.
• Rash.
• High blood prolactin (milk producing hormone) level (hyperprolactinaemia). This may uncommonly lead to symptoms such as breast enlargement, production of milk and menstrual disturbances.

Uncommon (affect between 1 in 100 and 1 in 1000 people)

• Sexual problems such as reduced sex drive and erectile dysfunction.
• Changes in appetite.
• Increased level of cholesterol in the blood.
• Confusion.
• Nightmares.
• Drop in blood pressure causing dizziness that occurs when moving from a lying down or sitting position to sitting or standing - see warning section above.
• Sensation of spinning.
• Sensation of ringing, or other noise in the ears (tinnitus).
• Dry mouth.
• Blurred vision, dry eyes, conjunctivitis.
• Muscle spasms.
• Stiff or aching joints.
• Skin reactions such as nettle rash (hives), eczema, dry skin, acne and itching.
• Abnormal heart rhythm seen as a 'prolonged QT interval' on a heart monitoring trace or ECG.
• Irregular heart beat called atrial fibrillation.
• Awareness of heartbeat (palpitations).
• Shortness of breath.
• Tardive dyskinesia (see warning section above).
• Tingling, pins and needles or numb sensations.
• Convulsions.
• Problems with speech.
• Decreased numbers of blood cells in the blood (see warning section above).
• Infections.
• Abnormally frequent urination, painful urination or urinary incontinence.

Rare (affect between 1 in 1000 and 1 in 10,000 people)

• Neuroleptic malignant syndrome (see warning section above).
• Problem with eye movement such as rolling of the eyes into the back of the head.
• Watery or red eyes.
• Bruising, inflammation, cysts or abscess at site of injection.
• Blood clot in the leg or the lungs (thromboembolism) – see warning section above.
• Prolonged erection in men. (If you get an erection that lasts longer than four hours (priapism) having these injections, you should consult a doctor immediately. Treatment of this condition should not be delayed more than six hours, as this can cause damage to the erectile tissue in the penis and irreversible erectile dysfunction.)
• Problems with body temperature control – see warning section above.

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while having treatment with this one, to make sure that the combination is safe.

There may be an increased risk of drowsiness and sedation if paliperidone is used with any of the following (which can also cause drowsiness):

• alcohol
• tricyclic antidepressants, eg amitriptyline
• strong opioid painkillers, eg morphine, codeine, dihydrocodeine
• benzodiazepines, eg diazepam, temazepam
• sedating antihistamines, eg chlorphenamine, hydroxyzine
• sleeping tablets, eg zopiclone.

Paliperidone may enhance the blood pressure-lowering effects of medicines that lower blood pressure, including medicines used to treat high blood pressure (antihypertensives) and medicines that lower blood pressure as a side effect, eg benzodiazepines. If you are taking medicines that lower blood pressure you should tell your doctor if you feel dizzy or faint after starting treatment with this medicine, as your doses may need adjusting.

There may be an increased risk of an abnormal heart rhythm, seen as a ‘prolonged QT interval’ on an ECG, if other medicines that can have this effect are used by people treated with paliperidone. These medicines include the following:

• antiarrhythmics (medicines to treat abnormal heartbeats), eg amiodarone, procainamide, disopyramide, sotalol
• the antihistamines astemizole, mizolastine or terfenadine
• arsenic trioxide
• atomoxetine
• certain antidepressants, eg amitriptyline, imipramine, maprotiline
• certain antimalarials, eg halofantrine, chloroquine, quinine, mefloquine, Riamet
• certain other antipsychotics, eg thioridazine, haloperidol, sertindole, pimozide
• cisapride
• dronedarone
• droperidol
• intravenous erythromycin or pentamidine
• methadone
• moxifloxacin
• saquinavir.

There may also be an increased risk of a prolonged QT interval if medicines that can alter the levels of salts such as potassium or magnesium in the blood, eg diuretics such as furosemide, are taken in combination with paliperidone.

Paliperidone may oppose the effect of medicines for Parkinson's disease that work by stimulating dopamine receptors in the brain, for example levodopa, ropinirole, pergolide, bromocriptine.

Paliperidone may oppose the effect of anticonvulsant medicines used to treat epilepsy.

Paliperidone may increase blood sugar levels and disturb the control of diabetes. People with diabetes may need an adjustment in the dose of their antidiabetic medication.

Paliperidone may oppose the effect of histamine (used to treat leukaemia) and is not recommended for people having this treatment.

The following medicines may speed up the breakdown of paliperidone in the body and so could make it less effective. If you take any of these medicines your doctor may need to increase your dose of paliperidone:

• carbamazepine
• rifampicin
• the herbal remedy St John's wort (Hypericum perforatum).

Other medicines containing the same active ingredient

• Invega

Last updated 19.07.2012

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