By Prof. Levine
In these two research trials we explored whether very high dose intravenous valproate or fosphenytoin might have rapid effects [within 20 minutes] on mania equivalent to the effects reported with these drugs in status epilepticus.
Phrolov K, Applebaum J, Levine J, Miodovnick H, Belmaker RH. Single-dose intravenous valproate in acute mania. J Clin Psychiatry. 2004 Jan;65(1):68-70
OBJECTIVE: High-dose loading with oral and intravenous valproate has been reported to be therapeutic in mania over 48 to 72 hours. We hypothesized that very high dose intravenous (IV) valproate might have even more rapid effects equivalent to effects in status epilepticus that occur within 20 minutes.
METHOD: Seven patients with mania (Young Mania Rating Scale score > 20) and minimal prior drug treatment were given valproate 20 mg/kg IV over 30 minutes.
RESULTS: No antimanic effects were observed during 120 minutes of observation. There were no side effects.
CONCLUSION: Slowly evolving biochemical changes, perhaps at the gene level, may be required for the antimanic effect of anticonvulsants.
Applebaum J, Levine J, Belmaker RH. Intravenous fosphenytoin in acute mania. J Clin Psychiatry. 2003 Apr;64(4):408-9
OBJECTIVES: Since several anticonvulsants are therapeutic in mania and since acute mania requires rapid and intensive treatment, we hypothesized that intravenous high-dose phenytoin might be acutely antimanic. A new prodrug of phenytoin, fosphenytoin, which has few cardiac or local vein side effects, was used to test this hypothesis.
METHOD: Seven patients with a DSM-IV manic episode and minimal prior drug treatment were given intravenous fosphenytoin and were assessed at baseline and after 15, 30, 45, and 60 minutes with the Young Mania Rating Scale, the Clinical Global Impressions scale, and the Mini-Mental State Examination. Data were gathered in 2002.
RESULTS: No antimanic effects were observed. No subject had any clear improvement in manic symptoms on the YMRS at any timepoint assessed.
CONCLUSION: Intravenous fosphenytoin at doses that are effective in status epilepticus appears to be ineffective in acute mania.
Stanley Research Center, Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.
By Prof. Levine
Did you hear about Prof. Seymour Antelman's idea of "Time Dependent Sensitization"?
If so, or if the concept makes you curious, then you are welcome to read this article.
By Prof. Levine
Written by Joseph Levine M.D. M.Sc, Yoram Barak M.D., and Ilana Granek M.A.
ABSTRACT
Psychotherapy with paranoid schizophrenics is a hard and often unrewarding task. Individual and group therapies are usually supportive and not aimed at changing the paranoid mode of thinking. Although cognitive therapy has been applied in schizophrenic patients it has not gained wide acceptance.
Cognitive dissonance postulates that individuals experience discomfort and tension when holding two dissonant beliefs simultaneously. We present group therapy of six schizophrenic paranoids treated by modified cognitive group therapy implementing cognitive dissonance as the vector of change. A control group of six age and sex matched paranoid schizophrenics were treated by supportive group therapy. Analysis of results, using the PANSS, during therapy and at follow up of four weeks demonstrates; statistically significant improvement of total PANSS score and positive symptoms subscale.
We call for further studies implementing cognitive dissonance strategies in the treatment of psychotic patients.
To download the entire article in Word format, click here.
By Prof. Levine
As early as 1952, in one of the earliest studies of psychotherapy treatment, the psychologist Hans Eysenck reported that two-thirds of patients either improved significantly in response to psychotherapy or recovered spontaneously while waiting for treatment with psychotherapy within a period of two years.
Some half a century later, the psychologist James W. Pennebaker, showed that a group of subjects who devoted 20 minutes daily recording in a diary their deepest feelings about the loss of a job fared better in a variety of outcome measures than either those who noted how they spent their time each day or those where no record was required. Various other studies involving different groups of patients where a similar task was used showed the same results (see Smyth & Pennebaker, 2008).
Wampold et al (Wampold ,2005) in a re-analysis of psychotherapeutic trials claimed that the use of psychological placebos may demonstrate a level of effectiveness which may occasionally attain that of accepted psychotherapies. Wampold et al (Wampold ,2007) also stated that no single treatment modality is superior in efficacy, and proposed that different psychotherapies have common factors [elements] which seem to account for much of the variance in outcome measures rather than specific techniques or modalities.
We suggest that two basic elements of psychotherapy, namely re-organization (of mental representation, metal operations or its output as behavior etc.) and association (via the repeated activation of two mental operations at the same time), are common not only to traditional psychotherapies but also to those waiting for psychotherapy, to certain forms of diary writing, and to the follow-up of patients receiving placebo psychotherapy.
Recently two intellectual giants have paved future avenues for psychotherapy research, approaching this subject from different angles.
The first is Isaac Marks, one of the founding fathers of behavioral therapy for anxiety disorders. Marks recently reviewed the research literature describing brief psychotherapies for anxiety and depressive disorders (Marks, 2002). This author stated that: " Brief behavioral, interpersonal, cognitive, problem-solving and other psychotherapies have a mature ability to improve anxiety and depressive disorders reliably and enduringly, often only with instruction from a manual or a computer. However we know little about which treatment components produce improvement, how they do so and why they do not help all sufferers"……" Therapy is coming of age regarding efficacy for anxiety and depression, but is only a toddler regarding the scientific principles to explain its effects". Marks himself suggested the existence of three components: relevant exposure (to environmental stimuli), introceptive exposure (to bodily stimuli) and cognitive restructuring.
Marks called for further research of these components of treatment. While agreeing with Marks, we suggest that these components are based on more basic elements.
The second giant is Eric Kandel, a memory researcher and Nobel laurent, who recently stated: "What our study group is discussing is whether or not the time is ripe to use brain imaging to evaluate the outcome of psychotherapy. There are now two forms of psychotherapy that have been medically proven to be effective. One is cognitive behavioral therapy…… the other is interpersonal therapy….Those are two scientifically validated forms of short-term therapy….we want to see whether there is a science here…" (Dobss, 2007)
However, exploring the brain changes associated with the therapeutic effects of proven psychotherapies as a whole will not advance the knowledge as to the specific brain changes induced by basic treatment elements.
In analogy with the search for endophenotypes for complex genetic disorders, we suggest that once the basic elements have been determined, the time will be ripe to look for the biology of these elements.
Thus it seems more logical first to determine and validate via research the basic elements of psychotherapy, and only thereafter to explore the therapeutic effects of these elements on the brain using a variety of imaging techniques.
What basic elements should be researched?
We propose that such basic elements should fulfill 3 criteria:
- They appear to be present in most practiced therapies and certainly in those with proven therapeutic outcomes
- They should be simple and not be based on purely theoretical grounds, enabling them to serve as building blocks for more sophisticated therapeutic maneuvers
- They should be in accordance basic principles of brain functioning.
In this regard the 2 basic elements we propose here, namely association and re-organization depend on the following principles of brain functioning respectively:
A] Hebbian learning: "Neurons that fire together wire together." commonly referred to as Hebb's Law (Hebb, 1961).
B] Neuroplasticity (variously referred to as brain plasticity or cortical plasticity or cortical re-mapping) which refers to the changes that occur in the organization of the brain as a result of experience (see Buonomano & Merzenich, 1998).
Prof. Joseph Levine, M.D. is an emeritus associate professor in the Division of Psychiatry, Faculty of Health Sciences, Ben Gurion University in Israel. Prof. Levine is a certified psychiatrist with clinical experience in controlled trials of adult psychiatric disorders and in psychotherapy. He was awarded a NRSAD independent investigator grant for the study of Creatine Monohydrate in psychiatric disorders -- mainly Schizophrenia. He resides and treats patients in Tel Aviv and all of central Israel.
