SOCIALIZATION FACTOR (PART 7)

DESCRIPTION OF PROSOCIALIZATION MEDICATIONS

7-A) Atypical antipsychotics – medications that are both stabilizing and prosocializing. These medication are stabilizing for psychosis and also are stabilizing to treat and prevent manic-like disinhibition. They increase socialization, but there is no evidence that the atypical antipsychotics have the property of causing persistent effects after discontinuation as do some other classes of medication. They vary widely from each other; they are classed together for two major reasons:

7-A1.a). They all treat the psychosis (positive symptoms) and the social withdrawal (negative symptoms) of Schizophrenia.

7-A1.b) They all block dopamine and Serotonin-2 receptors.

7-A1.c) There are six atypicals available in America. Although they all have some prosocializing properties, they can conveniently be divided into two groups of 3 non-activating and 3 activating.

7-A2) Non-activating atypicals: olanzapine/ Zyprexa, quetiapine /Seroquel, clozapine/ Clozaril. These are the safest of this class to protect against psychotic or manic activation, but there are some individuals who can be over-activated by the other two and need the absolute antipsychotic action of the older, typical antipsychotics such as haloperidol/ Haldol.

7-A2.a) Olanzapine/ Zyprexa. This is a very useful medication for rapid treatment of many agitated states. It has good antipsychotic action, is sedating and does not cause movement side effects often. It has a moderate benefit for socialization but can occasionally cause too much social activation. One autistic 11 year old. who is on haloperidol /Haldol after a psychotic reaction to mecamylamine/ Inversine has gained some socialization skills taking 0.625 mg every three days – but he cannot tolerate a higher dose. Olanzapine/ Zyprexa is considered the most likely of the commonly used atypicals to cause weight gain and increase the potential for the occurrence of diabetes.

7-A2.b) Quetiapine/ Seroquel. Rarely activating, rare movement side effects. Especially helpful with post-traumatic type aggressive reactions, social withdrawal, irritability, negative thoughts and dreams; but not too socially brightening. Antipsychotic action not very strong until does are fairly high.

7- A2.c) Clozapine/ Clozaril. The best for severe violent psychotic aggression. Increases socialization, but is minimally brightening and never disinhibiting. Very rare movement side effects. Individuals once stabilized on clozapine/ Clozaril sometimes can become socially brighter when small doses of an activating atypical is added.
Note that clozapine/ Clozaril is less used because it has numerous side effects and requires regular blood counts to check for low white cell level.

7-A3) The activating atypical antipsychotics: risperidone/ Risperdal, ziprasidone/ Geodon, aripiprazole/ Abilify all can produce increased socialization – especially at low doses. This effect seems to be lessened at higher doses where the basic dopamine-blocking antipsychotic action is more dominant. Thus at high doses these medications can be used successfully to treat mania, but at low doses can cause manic-like social disinhibition. (see case 2). The difference between high and low dose effect may also explain why the clinicians who use a high dose regime of these medications state that they help autistic individuals’ aggression and hyperactivity but do not see the benefits for their social withdrawal. These medications do have some distinct differences

7-A3.a) Risperidone/ Risperdal is moderately activating, but is also has the strongest dopamine blocking effect. This means more side effects such as movement disorders and elevated prolactin, but perhaps more true antipsychotic effect at low doses. It comes in many different sized tablets and also liquid—making it the easiest to use for initiating therapy at very low doses.

7-B2.c) Aripiprazole/ Abilify. This drug has a unique combination of dopamine blocking and stimulation (partial dopamine agonism.) It definitely has more social brightening activity than any other atypical antipsychotic. In fact, in some individuals it has apparently been more activating than mecamylamine/ Inversine. Since it takes several days to be eliminated from the body, low doses are most easily achieved by starting on a twice a week schedule. However, some individuals become excessively activated after taking just 2.5 mg (half of 5mg tablet), which is the lowest easily obtainable dose using tablets. The liquid form is now available but a bottle is over $200. It has demonstrated positive prosocialization in a multihandicapped 7 year old at a dose of 2 drops every other day, but caused irritability in that child at 2 drops daily. It was also too activating when used in place of risperidone/ Risperdal in an autistic child of six.

7-C). Non-antipsychotic Prosocialization Meds.

7-C1) The glycine-MNDA modulators.
These medicines have been discussed in length. The findings of the glycine agonists’ effect on negative symptoms of schizophrenia represented a major breakthrough in understanding that treatment of prosocialization effects is different from treatment of other symptoms.

7-C1.a) The glycine agonists. These are not being used routinely for various reasons—D-serine is not readily available;

7-C1.a1) L-glycine requires very large doses which are difficult to tolerate; D-Cycloserine must be repackaged to make smaller doses. One of the original researchers, Dr. Heresco-Levy of Israel apparently is still using L-glycine in some schizophrenic patients..

7-C1.a2) D-cycloserine (partial D-serine receptor agonist)
Standard dose for Tuberculosis- 500 mg/d.
Standard dose for Schizophrenia- 50 mg/d.
Starting dose in this clinic for Autism- 12 mg/day. In this clinic’s experience, the d-cycloserine dose should start at a very low dose in autism, but Dr Davis of Emory University uses up to 500 mg to help in behavioral retraining for phobia

7-C1.a3) D-serine Not available in USA. No experience, but in countries where it is available it seems ideal for prosocialization therapy in individuals without evidence of underlying psychotic problems. There is amazingly little written about its use.

7-C1.b) NMDA-acting medications. It is a paradox that medication with various actions on NMDA such as the indirect agonists and partial antagonists seem to improve conversational capacity. One possibility is that both classes of medications help regulate the receptor—making it more efficient –although they do it by different mechanisms.

7-C1.b1) memantine/ Namenda. This partial NMDA antagonist is readily available and seems to be well tolerated. There are occasional Alzheimer’s patients who become agitated when given the recommended titration of 5 mg increases every week up to 20 mg/day, but a number do tolerate this schedule. There is a significant number who become more socially interactive and there are the reports previously listed of its treating catatonic withdrawal – with improvement occurring within 24 hours. Experience in patients with other diagnoses is very limited, but one 20+ year old autistic male spoke several complex 6- 10 word sentences for the first time after being placed on 1.25 mg of memantine/ Namenda. One Alzheimer’s patient was able to discontinue a previously necessary low dose of the antipsychotic haloperidol/ Haldol after achieving improved socialization and conversation with memantine/ Namenda.

7-C1.b2) acamprosate/ Campral. (NMDA antagonist and GABA agonist?) Used to reduce cravings after alcohol detoxification. It may be less activating than Namenda. It comes in 333 mg controlled release tablets to increase the absorption into gut. Standard dose 2 tabs 3xday.
Starting doses used ½- 1 tab daily or every other day. Has produced very significant sustained prosocializing effects but also excessive activation and gastrointestinal symptoms

7-C1.b3) lamotrigine/ Lamictal.(inhibitor of Glutamate release) This anticonvulsant, which has documented mood-stabilizing properties, seems to have antidepressant action and may precipitate mania on occasion. There are reports, as yet unconfirmed, that it may have demonstrated prosocialization properties. One of its effects is slowing the release of glutamate. It will be interesting to find out if there is any validation of this possible relationship.

7-C1.b4) Dextromethorphan. This anti-cough medicine is available over the counter as Delsym, which is supposed to last 12 hours. Only recently it is being tried in small doses with those who are disinhibited by other MNDA active meds.

7-C1.b4/a) It is to be noted that dextromethorphan needs to be converted into a morphine-like drug to be a good cough suppressant. It is also known that some drug abusers prevent this change with paroxetine/ Paxil or fluoxetine/ Prozac – thus getting MNDA activity. It is possible that only the unchanged drug has prosocialization properties-- thus benefit may be most likely for individuals also on paroxetine/ Paxil or fluoxetine/ Prozac or those with deficient enzyme activity. Currently there is no answer whether it is necessary to block the change; however elderly with dementia have sometimes been calmed on two teaspoons of the syrup alone.

7-C1.c) mecamylamine/ Inversine (non-competitive nicotinergic antagonist.) A very potent stimulator of social conversation. This effect is surprising that a nicotine blocker has this action since nicotine receptors generally activate brain processes. As with the glycine agonist and atypical antipsychotics, the starting dose for prosocialization effect often may be very low compared to other uses. ( e.g. 0.25 mg for two days)

7-C1.c1. Side effects. Of the various prosocialization medications, mecamylamine/ Inversine seems to have more occurrences of psychotic and overactivity behavioral side effects

7-C1.c2) Sample doses. Standard dose for Hypertension- 5 to 25 mg/d.
Standard dose for Tourette’s- 2.5 to 7.5 mg/d. Starting dose for Autism or other social inhibition: 0.25mg to 1.25mg 2 successive days then 5 days off. Raise slowly up to 5 mg/d. If benefit is seen do not raise dose for a time.

7-D) Other medications with activating and possible prosocialization properties. There needs also to be considered other medications which affect social activation.

7-D1) Alcohol and Benzodiazepines - anti-anxiety meds. It is a common experience that some people become socially and conversationally disinhibited under the influence of alcohol or the “tranquilizers” like diazepam/ Valium. There are also a few individuals who become pathologically violent when they are under the influence of such substances. But these changes seem to last only during the influence of the substance, and do not have prolonged effects.

7-D2) Antidepressants – The older tricyclic antidepressants were known for precipitating manic-like states and making the cycles occurs more often (rapid cycling) The fluoxetine/ Prozac class of antidepressants, (called SSRI’s) can also cause swings into manic-like activity in true bipolar individuals – and in others who have “mood swings” from other causes such as Post Traumatic Stress Disorder, and personality disorders.(The possible danger of inducing mania and rapid cycling in bipolar disorder is a main concern about prescribing antidepressants. According to the concept that bipolar swings are the changing of dissociatively suppressed drives, this would presume that the effect of the antidepressant was on dissociation.) A history of unwanted activation from these medicines frequently, but not always, predicts a negative outcome to an attempt to use the more socially activating medications such as aripiprazole/ Abilify and mecamylamine/ Inversine.

7-D3) Stimulants: methylphenidate/ Ritalin, Adderall, (cocaine is also a stimulant). Before the arrival of atypical antipsychotics, there was some belief that stimulants could help the negative symptoms of schizophrenia – but benefits, if any, were rare. These medications do have a tendency to open up psychotic reactions in a certain percentage of individuals. Some patients with Attention Deficit Disorder may have a good response for the first few weeks and then become rampantly psychotic until the stimulant is discontinued. These medications need to be given carefully to individuals with a history suggesting the possibility of developing psychosis or mania.

7-D3.a) Awakeness medications – modafinil/ Provigil. This is a non-stimulant medication that is indicated to maintain wakefulness. It also has been used in ADHD. There are reports of its demonstrating prosocialization effects in developmental disabled individuals.

7-D4) Chemicals which may relate to prosocialization effects.
There are two functioning body chemicals which have demonstrated effects which enhance socialization. Their actual role in prosocialization treatment is not known.

7-D4.a) Oxytocin. The pituitary hormone oxytocin which is known for acting differently in one species of rodents than another. In the prairie vole, which are monogamous, oxytocin affects certain areas of the brain. The mountain vole is promiscuous and affected in different brain areas.

7-D4.b) PEA (phenylethylamine) This is a relative of noradrenaline but very short-lived in the body. There is speculation that it affects certain euphoric love feelings. It is used by the drug culture and has occasionally been mentioned as a treatment for depression. One clinician (Hector Sabelli) attempted to spark interest in this compound as a factor in illness, but generally psychiatry has ignored it.

7- D5) Elimination of the “Antisocialization medicine” phenytoin/ Dilantin. This anticonvulsant medication has earned the reputation in this clinic of causing social rigidity. This older anticonvulsant is known not to have benefits as a mood stabilizer and is therefore not used by psychiatrists. However, neurologists and other physicians continue to use it and seem unaware of the negative effects that it causes to some patient’s socialization ability. There are a number of individuals in madisondoctrine’s care who have been changed from being socially negative, rigid, and a source of friction in their homes to being socially agreeable simply by being taken off phenytoin/ Dilantin. Sometimes these individuals have been on the phenytoin/ Dilantin for more than twenty years. It is the position of madisondoctrine that nearly every one on phenytoin/ Dilantin should be given a trial being on a different anticonvulsant.

7-D5.a Elimination or lowering of typical antipsychotic or high dose atypical antipsychotic. Excessive doses of these Dopamine-blocking medication can cause mental and social dullness as it summarized in my saying

7-D5.b If a normally functioning person is on haloperidol/ Haldol
then roses look gray. But if roses look violently purple with bright orange rays coming
out of them, haloperidol/ Haldol can make them look red.