Can Formal THought Disorder Be Treated?

Dr. Saltzman:

Is "formal thought disorder" treatable? 

[name withheld] 











Dear [name withheld]: 

Surprisingly, to me at least, I get more ask the psychologist letters on this topic than on any other except for the eternal questions about penis size.

Formal thought disorder is one of the symptoms of schizophrenia. Generally, symptoms of schizophrenia fall into four basic categories. First there are the behavior disorders such as catatonia in which the ill person may hold the same position for hours on end, unable to speak or to eat. A second category of schizophrenic symptoms involves disturbances to feeling and emotion, the classic one of these being so called "flat affect," in which events that in normal people would produce obvious emotional responses (very good news, for example, or sudden death of a loved one) produce no emotional response at all. A third category of schizophrenic symptoms is disorders of perception such as hearing voices or seeing things which are not apparent to healthy people. Finally, there is the collection of symptoms called "formal thought disorder." 

















In formal thought disorder, people may give voice to strange or unrealistic thoughts. These may reach the level of fixed delusions such as the idea that a government agency has a way of implanting thoughts in one's mind, that hidden cameras are recording every movement, or that one is endowed with special, superhuman powers. Often in formal thought disorder the disturbed thinking becomes obvious to observers through speech or writing that sounds strange or disconnected, even to the point of being impossible to understand. 
















Nancy Andreasen* has broken down into subcategories examples of the disordered speech associated with formal thought disorder. I take the liberty of quoting them here:

• Pressure of speech - An increase in the amount of spontaneous speech compared to what is considered customary.
• Distractible speech - During mid speech, the subject is changed in response to a stimulus. e.g. "Then I left San Francisco and moved to... where did you get that tie ?"
• Tangentiality - Replying to questions in an oblique, tangential or irrelevant manner. e.g. "What city are you from ?", "Well, that's a hard question. I'm from Iowa. I really don't know where my relatives came from, so I don't know if I'm Irish or French".
• Derailment - Ideas slip off the track on to another which is obliquely related or unrelated. e.g. "The next day when I'd be going out you know, I took control, like uh, I put bleach on my hair in California".
• Incoherence (word salad) - Speech that is unintelligible due to the fact that, though the individual words are real words, the manner in which they are strung together results in incoherent gibberish, e.g. the question "Why do people believe in God?" elicits a response like "Because make a twirl in life, my box is broken help me blue elephant. Isn't lettuce brave? I like electrons, hello."
• Illogicality - Conclusions are reached that do not follow logically (non sequiturs or faulty inductive inferences).
• Clanging - Sounds rather than meaningful relationships appear to govern words. e.g. "I'm not trying to make noise. I'm trying to make sense. If you can't make sense out of nonsense, well, have fun".
• Neologisms - New word formations. e.g. "I got so angry I picked up a dish and threw it at the geshinker".
• Word approximations - Old words used in a new and unconventional way. e.g. "His boss was a seeover".
• Circumstantiality - Speech that is very delayed at reaching its goal. Excessive long-windedness.
• Loss of goal - Failure to show a chain of thought to a natural conclusion.
• Perseveration - Persistent repetition of words or ideas. e.g. "I'll think I'll put on my hat, my hat, my hat, my hat, my hat, my hat, my hat, my hat..."
• Echolalia - Echoing of other people's speech e.g. "Can we talk for a few minutes?", "Talk for a few minutes".
• Blocking - Interruption of train of speech before completed.
• Stilted speech - Speech excessively stilted and formal. e.g. "The attorney comported himself indecorously".
• Self-reference - Patient repeatedly and inappropriately refers back to self. e.g. "What's the time?", "It's 7 o'clock. That's my problem".
• Phonemic paraphasia - Mispronounciation; syllables out of sequence. e.g. "I slipped on the lice broke my arm".
• Semantic paraphasia - Substitution of inappropriate word. e.g. "I slipped on the coat, on the ice I mean, and broke my book".

If a person falls into a sustained period of formal thought disorder, and if the symptoms are serious enough so that even a determined and sympathetic person cannot understand the speech, writing, or other communications of the ill person, you will understand that the ill person is now lost in a world of his or her own, unable to understand or be understood by people living in the ordinary world of consensual reality. This is total and complete isolation; a lonelier state cannot be imagined. 
















Now, you ask if formal thought disorder can be treated. This is the same, you see, as asking if schizophrenia can be treated. The answer is yes. Not only can schizophrenia be treated, but it must be treated, and treated promptly and aggressively, because schizophrenia is a progressive condition which almost always worsens with time so that without treatment the schizophrenic person will likely end up totally disabled, often requiring custodial care merely in order to survive. 















Before beginning treatment of schizophrenia, it is important to rule out organic factors, such as brain tumor, which can produce the same kinds of symptoms as schizophrenia. Once these are ruled out, treatment usually involves trying to stabilize the patient, in other words, to bring the patient back into some useful contact with reality, and then trying to prevent relapses. 

Since we still do not know the etiology (the causes) of schizophrenia--the best contemporary thinking blames a genetic predisposition (an inborn imbalance of brain chemistry, that is) later potentiated by environmental factors such as family pressures--it cannot be said that there is a cure for schizophrenia, or even that a cure is in the offing. In other words, so far it is not known what schizophrenia really is, much less how to cure it. This leaves aggressive treatment of symptoms as the only option. The best treatment involves suppression of symptoms with such medicines as haloperidol decanoate (Haldol Decanoate) or fluphenazine decanoate (Prolixin Decanoate), combined with counseling and psychotherapy aimed at helping the patient to understand and deal with his or her situation. 
















If you or anyone you care for shows symptoms of schizophrenia, whether they be disordered thinking, or any of the other indications, I urge you to seek expert advice immediately. You should begin with a visit to a physician who will move to rule out organic causes. Once these are ruled out, your physician will be able to arrange for the expert psychiatric care needed in all cases of schizophrenic illness. 

Be well. 


_____________________________________


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

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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