Responsible:
Prof. Hannelore Ehrenreich, MD, DVM
Clinical Neuroscience
Max-Planck-Institute of Experimental Medicine
Hermann-Rein-Strasse 3
D-37075 Göttingen
Tel: ++49-551-3899-628
Fax: ++49-551-3899-670
Email: ehrenreich@em.mpg.de
 

 

 
 
 
 
 
 
 
 


OLITA - Outpatient Longterm Intensive Therapy for Alcoholics:
A novel program for the treatment of severely affected chronic alcoholics


 

OLITA, the Outpatient Longterm Intensive Therapy for Alcoholics, is a comprehensive research project on the treatment of alcoholism which started in 1993. The active therapeutic part of this monocentric pilot study in Göttingen has been terminated successfully in summer 2003 after 10 years and the completion of 180 patients. At present, a multicenter OLITA project is under planning for which, however, financing has unfortunately not yet been found, despite most intensive negotiations with health care providers and proposals to potential public funding agencies. This multicenter study will pursue two major aims: (1) To reproduce the unusually high success of this treatment program for alcoholics in other centers under strict quality control and sound economical evaluation. Therefore, the "franchising procedure" will be applied (see below). (2) To exploit the multicenter setting for the systematic investigation of psychological and biological determinants of treatment outcome.
The OLITA project was supported by a two-year grant of the Ministry of Labor and Social Services, Lower Saxony, Germany, and has recently been awarded with a three-year grant of the German Ministry of Health (Bundesministerium für Gesundheit und Soziale Sicherung BMGS).


THE OLITA PROGRAM

OLITA is a novel biopsychosocial treatment program for severely affected chronic alcoholics extending over two years following inpatient detoxification. Major elements of the treatment program are: (1) Frequent contacts, initially daily, with a slow reduction of contact frequency up to the end of the second year; (2) Rotation of therapists; (3) Support of social reintegration and aggressive aftercare; (4) Induction of alcohol intolerance through application of inhibitors of acetaldehyde dehydrogenase; (5) Explicit control (supervised intake of deterrent medication and regular urine analysis for alcohol).

THE MAIN THERAPEUTIC ELEMENTS OF OLITA

l High frequency shortterm individual therapeutic contacts
Structured, guarded attachment by supportive, non-demanding shortterm contacts; initially 15 minutes daily, including weekends and holidays; slow tapering off contact frequency aiming at regular and permanent attendance of weekly group sessions.
l Emergency service and crisis interventions
In case of emergency patients and their relatives can contact OLITA round the clock on any day of the year.
l Social re-integration and home visits
Specific assistance in re-arranging a social network which supports an abstinent lifestyle;
explicit cooperation with family members and friends; family and marital sessions; advice and support regarding occupation, authorities, housing problems, moving, job seeking, financial and legal problems.
l Induction of alcohol intolerance
Use of disulfiram (Antabuse ®), so-called deterrent medication (inhibition of the alcohol-metabolizing enzyme acetaldehyde dehydrogenase leads in case of alcohol consumption to accumulation of toxic acetaldehyd resulting in an "inner poisoning", the so-called "disulfiram-ethanol reaction", comprising extensive flushing, hyper- or hypotension, tachycardia, nausea, vomiting, anxiety).
l Introduction of control factors
Regular urine and blood analyses for alcohol and other drugs of abuse; if necessary, additional breath tests. Supervised intake of deterrent medication and explicit exploitation of its psychological effects.
l Aggressive aftercare
Aggressive therapeutic interventions to immediately interrupt beginning and to prevent threatening relapses: Patients who miss a therapeutic contact are called on to continue therapy or to restart abstinence; examples for aggressive aftercare are spontaneous house visits, telephone calls and involvement of close friends / relatives.
l Therapist rotation
An interdisciplinary cooperating team of 6-7 therapists is treating the patients (supervising psychiatrist, psychologist, physician, social worker, nurse and MD or PhD students). All therapists are equally responsible for all patients. The classical fixation of a single patient to a single therapist is abandoned.

PRACTICAL REALIZATION OF THE THERAPEUTIC PROGRAM

l Inpatient period: Detoxification
2-3 weeks; daily individual sessions, 15 minutes each;
disulfiram, 100 mg daily.
l Outpatient period I: Intensive phase
3 months; daily individual sessions, 15 minutes each;
disulfiram, 100 mg daily.
l Outpatient period II: Stabilizing phase
3-4 months, according to individual need; 3 times a week individual sessions,
15 minutes each; disulfiram, 400 mg, 3 times a week.
l Outpatient period III: Weaning-off phase
6 months; twice a week individual sessions, 30 minutes each;
disulfiram, 400 mg, twice a week.
l Outpatient period IV: Aftercare phase
12 months; once weekly group session; initially weekly individual sessions (30 minutes) which are gradually reduced; disulfiram, 400 mg, once a week; tapering off between months 13 and 20, individual extension possible.

PATIENTS IN THE OLITA PROGRAM

Sociodemographic and addiction severity characteristics
Thus far, 180 alcoholics (144 men, 36 women) have been treated with a follow-up success rate of over 50% abstinent patients despite a "negative selection",
with regard to severity of alcohol dependence, co-morbidity, and social detachment, upon entering the program. Patients were on average 44 ± 8 years old, had a duration of alcohol dependence of 18 ± 7 years, approximately 7 ± 9 prior inpatient detoxification treatments and 1 ± 1 failed inpatient longterm therapy. Almost 60% of the patients were unemployed. Psychiatric co-morbidity (diseases in addition to alcoholism) amounted to 80%. About 60% of the patients suffered from severe sequelae of alcoholism (e.g. polyneuropathy, chronic pancreatitis, liver cirrhosis (Figure 1)).

Longterm drinking outcomes
Considering this severely affected population of alcoholics, the longterm success rate of OLITA is incredibly high: More than 50% of the patients remain abstinent over up to 7 years of post-treatment follow-up (Figure 2). In the literature, abstinence rates of usually less than 30% at follow-up periods of less than a year (rarely over 2 years) are reported.

Fig. 2: The cumulative abstinence probability during the 9-year study is .52 for the complete sample (N=180)


(Kaplan-Meier estimates; cases are censored if they have not experienced a relapse by the end of follow-up).


A case control study
Compared with thoroughly paralleled case controls who participated in alternative treatment programs, the outcome of OLITA patients is significantly better (Figure 3). Separate analysis of lapses (intake of alcohol followed by immediate cessation of drinking and continuation of the OLITA program) and relapses (intake of alcohol followed by "malignant" continuation of drinking) in OLITA patients reveals that the "true relapse rate" in OLITA patients is 30% as compared to 70% in controls. Relapses plus lapses in OLITA patients amounted to 60%. Thus, the immediate stop of lapses by means of crisis interventions has prevented the progression into relapses for 30% of the patients (Figure 3).

Fig. 3:


Mechanisms of recovery and irreversibility
The OLITA program offers the unique possibility to follow a well defined population of alcoholics over a long period of strictly controlled alcohol abstinence. In this ideal setting, we were able to study alcohol-induced pathology as well as kinetics and mechanisms of recovery. Topics investigated include chromosomal aberrations, hematopoietic factors and circulating blood cells, stress hormones, sexual function and sex hormones. Recently, we reported persistent alterations in many neuroendocrinological parameters, for example enduring disturbances of water / electrolyte homeostasis and thirst. These findings will prepare the ground for future pharmacological therapies. The underlying "mechanisms of irreversibility" may be directly or indirectly related to the phenomenon of dependence as well as of addictive behavior.


Success of OLITA and how to explain it ...
Based on the high abstinence rate of severely affected chronic alcoholics in the OLITA program, a tremendous improvement in psychological, biological and social parameters of this patient group could be achieved. The unemployment rate of OLITA patients declined to 22% in an area (Göttingen) with a general unemployment rate of 17% (Figure 4).

Fig. 4:


Figure 5 illustrates the highly significant reduction in psychiatric comorbidity. Shown are depression and anxiety disorders in per cent of the study population from month 1 of therapy to 2 years, i.e. the termination of the program.
Additionally, patients had a clear decrease in physical sequelae of alcoholism, ranging from liver disease to polyneuropathy.

Fig. 5:

PROCESS - OUTCOME RESEARCH ON OLITA

Apart from the regained quality of life of these patients, the general health care cost reduction is enormous.
How can we explain the unusual success of our very structured, intensive and comprehensive longterm treatment? A major "mechanism of action" of OLITA seems to be the therapist rotation. This element of OLITA represents a "revolution in psychotherapy". The fact that 6-7 therapists are equally responsible for each patient translated the ordinary two-way relation between therapist and patient into a most efficient multi-way therapeutic network. Therapists stick to the rules of the program and the ideas of alcoholism treatment realized within the concept (congruence) and frequently repeat these rules and ideas (repetition). Thereby, a variety of individual therapists with a variety of different thoughts create a therapeutic atmosphere characterized by vivid and multifaceted variation. We hypothesize that these specific factors activate common factors of psychotherapy and that, as an element of OLITA, therapist rotation has a major contribution to its success (Figure 6).

Fig. 6: Common and specific factors of OLITA


How to prove efficacy in a therapeutic setting?
In contrast to pharmacological agents, psychotherapeutic effects are much more difficult to define or measure. In addition, quality control for psychotherapy is widely missing. Therefore, and also to prove our hypotheses of how OLITA works, we have developed the video-assisted monitoring of psychotherapeutic processes in chronic psychiatric disease (VAMP). The steps involved in this monitoring are described in Figures 7 and 8.

Fig. 7: Development of the video-assisted monitoring of psychotherapeutic processes in chronic psychiatric disease (VAMP)


A total of 61 patients has been analyzed over the past 4 years using the VAMP. Each patient had 17 videotapes of psychotherapeutic sessions within the 2 years of OLITA recorded. These videos are the basis of both, a macroanalytic and a microanalytic evaluation of therapeutic processes and their influence on outcome.

Fig. 8: Video-recording of therapy sessions


Among the scales evaluated in VAMP are (1) common psychotherapeutic factors, (2) addictive behavior, (3) disease concept, (4) working atmosphere, (5) psychopathological symptoms, (6) therapeutic alliance and (7) problem solving. The scales of the VAMP show high interjudge reliability, high homogeneity, as well as a pronounced intercorrelation pattern of the specific factors which indicates good construct validity (Figure 9).

Fig. 9: Intercorrelation pattern of the VAMP scales

Construct validity: Both problem solving scales are strongly associated with the common psychotherapeutic factor "Analytic processing and reflexion". However, they are independent from each other.

 

Construct validity: The three therapeutic relationship scales are highly correlated. This intercorrelation pattern suggests an underlying common relationship factor.


Construct validity: As an example, the intercorrelation pattern of the relapse alertness (central construct) with common psychotherapeutic factors, specific factors of problem solving and addictive behavior is shown. Whereas relapse alertness is strongly correlated with analytic processing and reflexion, functional problem solving, statement about relapse risk and the disease concept, it is only weakly associated with implicit and explicit craving and nearly independent from both general and abstinence self-efficacy.


Where to go from here ...
Our current BMGS-funded research topics are: (1) The analysis of the role of deterrent medication for psychotherapeutic processes and longterm outcome of alcoholism treatment. (2) The employment of the VAMP in a prospective longitudinal study investigating processes of change during the first six months of OLITA. Associations between therapeutic processes and essential outcome variables (e.g. abstinence, relapse, addiction severity, course of comorbidity, neuropsychological regeneration) will be analyzed.


TRANSLATION OF OLITA ON THE BASIS OF FRANCHISING

For the translation of OLITA from a successful monocentric project into multicenter evaluation and later into routine health care, we suggest an expanded use of the so-called franchising as derived from economy (Figure 10). This is a novel approach within the health system and will certainly provide a socio-political challenge of general significance.

Fig. 10:


By franchising, evidence based (scientifically proven) concepts can be standardized for multicenter exploration and be continuously controlled for quality and success (Figure 11).

Fig. 11:



Relevant publications

1. Ribbe K, Ackermann V, Schwitulla J, Begemann M, Papiol S, Grube S, Sperling S, Friedrichs H, Jahn O, Sillaber I, Gefeller O, Krampe H, Ehrenreich H: Prediction of the Risk of Comorbid Alcoholism in Schizophrenia by Interaction of Common Genetic Variants in the Corticotropin-Releasing Factor System. Arch Gen Psychiatry. Aug 1. (2011).

2. Krampe H, Ehrenreich H: Therapeutic alliance and multiple psychotherapy in the context of therapist rotation: Experiences with OLITA Neurology, Psychiatry and Brain Research 18: 137-152 (2012).

3. Krampe H, Spies CD, Ehrenreich H: Supervised Disulfiram in the Treatment of Alcohol Use Disorder: A Commentary. Alcohol Clin Exp Res. 35: 1732-6 (2011).

4. Krampe H, Ehrenreich H: Supervised Disulfiram as Adjunct to Psychotherapy in Alcoholism Treatment. Curr Pharm Des. 16: 2076-90 (2010).

5. Krampe H., Stawicki S., Ribbe K., Wagner T., Bartels C., Kroener-Herwig B., Ehrenreich H.: Development of an outcome prediction measure for alcoholism therapy by multimodal monitoring of treatment processes. J Psychiatr Res. 43, 30-47 (2008).

6. Krampe H., Stawicki S., Hoehe M.R., Ehrenreich H.: Outpatient Long-term Intensive Therapy for Alcoholics (OLITA): a successful biopsychosocial approach to the treatment of alcoholism. Dialogues Clin Neurosci. 9, 399-412 (2007).

7. Bartels, C., Kunert, H-J., Stawicki, S., Kröner-Herwig, B., Ehrenreich, H., Krampe, H.: Recovery of hippocampus-related functions in chronic alcoholics during monitored longterm abstinence. Alcohol and Alcoholism 42 (2): 92-102, (2007).

8. Hasselblatt, M., Krampe, H., Jacobs, S., Sindram, H., Armstrong, V.W., Hecker, M., Ehrenreich, H.: Arginine challenge unravels persistent disturbances of urea cycle and gluconeogenesis in abstinent alcoholics. Alcohol and Alcoholism 4: 372-378, (2006).

9. Krampe, H., Wagner, T., Stawicki, S., Bartels, C., Aust, C., Kröner-Herwig, B., Küfner, H. and H. Ehrenreich: Personality Disorder and Chronicity of Addiction as Independent OutcomePredictors in Alcoholism Treatment. Psychiatric Services 57: 708-712, (2006).

10. Krampe H, Stawicki S, Wagner T, Bartels C, Aust C, Ruther E, Poser W, Ehrenreich H.: Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: impact of alcohol deterrents on outcome. Alcohol Clin Exp Res. 30: 86-95, (2006).

11. Wagner, T., Krampe, H., Stawicki, S., Reinhold, J., Jahn, H., Mahlke, K., Barth, U., Sieg, S., Maul, O., Galwas, C., Aust, C., Kröner-Herwig, B., Brunner, E., Poser, W., Henn, F., Rüther, E., Ehrenreich, H.: Substantial decrease of psychiatric comorbidity in chronic alcoholics upon integrated outpatient treatment - results of a prospective study. Journal of Psychiatric Research, 38: 619-635, (2004).

12. Spies, C.D., Von Dossow, V., Eggers, V., Jetschmann, G., El-Hilali, R., Egert, J., Fischer, M., Schroder, T., Hoflich, C., Sinha, P., Paschen, C., Mirsalim, P., Brunsch, R., Hopf, J., Marks, C., Wernecke, K.D., Pragst, F., Ehrenreich, H., Muller, C., Tonnesen, H., Oelkers, W., Rohde, W., Stein, C., Kox, W.J.: Altered Cell-mediated Immunity and Increased Postoperative Infection Rate in Long-term Alcoholic Patients. Anesthesiology, 100: 1088-1100, (2004).

13. Jahn, H., Döring, W., Krampe, H., Sieg, S., Werner, C., Poser, W., Brunner, E., Ehrenreich, H.: Preserved vasopressin response to osmostimulation despite lowered basal vasopressin levels in long-term abstinent alcoholics. Alcoholism Clinical & Experimental Research, 28: 1925-30, (2004).

14. Krampe, H., Wagner, T., Küfner, H., Jahn, H., Stawicki, S., Reinhold, J., Timner, W., Kröner-Herwig, B., Ehrenreich, H.: Therapist Rotation - A new element in the outpatient treatment of alcoholism. Substance Use & Misuse, 39: 135-178, (2004).

15. Ehrenreich, H., Krampe, H.: Does disulfiram have a role in alcoholism treatment today? Not to forget about disulfiram's psychological effects. Addiction, 99: 26-27, (2004).

16. Döring, W., Herzenstiel, M.-N., Krampe, H., Jahn, H., Pralle, L., Sieg, S., Wegerle, E., Poser, W., Ehrenreich, H.: Persistent Alterations of Vasopressin and N-Terminal Proatrial NatiureticPeptide Plasma Levels in Long-Term Abstinent Alcoholics. Alcoholism: Clinical and Experimental Research, 27: 849-861, (2003).

17. Hasselblatt, M., Krieg-Hartig, C., Hufner, M., Halaris, A., Ehrenreich, H.: Persistent Disturbance of the Hypothalamic-Pituitary-Gonadal Axis in Abstinent Alcoholic Men. Alcohol & Alcoholism, 38: 239-242, (2003).

18. Hornecker, E., Muus, T., Ehrenreich, H., Mausberg, RF.: A pilot study on the oral conditions of severely alcohol addicted persons. Journal of Contemporary Dental Practice, 4: 51-9, (2003).

19. Haber, H., Jahn, H., Ehrenreich, H., Melzig, M.F: Assay of salsolinol in peripheral blood mononuclear cells of alcoholics and healthy subjects by gas chromatography-mass spectrometry. Addiction Biology, 7: 403-407, (2002).

20. Schneider, U., Altmann, A., Baumann, M., Bernzen, J., Bertz, B., Bimber, U., Broese, T., Broocks, A., Burtscheidt, W., Cimander, K.F., Degkwitz, P., Driessen, M., Ehrenreich, H., Fischbach, E., Folkerts, H., Frank, H., Gurth, D., Havemann-Reinecke, U., Heber, W., Heuer, J., Hingsammer, A., Jacobs, S., Krampe, H., Lange, W., Lay, T., Leimbach, M., Lemke, M.R., Leweke, M., Mangholz, A., Massing, W., Meyenberg, R., Porzig, J., Quattert, T., Redner, C., Ritzel, G., Rollnik, J.D., Sauvageoll, R., Schläfke, D., Schmid, G., Schröder, H., Schwichtenberg, U., Schwoon, D., Seifert, J., Sickelmann, I., Sieveking, C.F., Spiess, C., Stiegemann, H.H., Stracke, R., Straetgen, H.D., Subkowski, P., Thomasius, R., Tretzel, H., Verner, L.J., Vitens, J., Wagner, T., Weirich, S., Weiss, I., Wendorff, T., Wetterling, T., Wiese, B., Wittfoot, J.: Comorbid anxiety and affective disorder in alcohol-dependent patients seeking treatment: The first multicentre study in Germany. Alcohol & Alcoholism, 36: 219-223, (2001).

21. Hasselblatt, M., Martin, F., Maul, O., Kernbach-Wighton, G., Ehrenreich, H.: Persistent macrocytosis in longterm abstinent alcoholics. JAMA, 286: 2946, (2001).

22. Hüttner, E., Matthies, U., Nikolova, T., Ehrenreich, H.: A follow-up study on chromosomal aberrations in lymphocytes of alcoholics during early, medium, and long-term abstinence. Alcoholism, Clinical and Experimental Research, 23: 344-348, (1999).

23. Schmitt, M., Gleiter, C.H., Nichol, J.L., Pralle, L., Hasselblatt, M., Poser, W., Ehrenreich, H.: Haematological abnormalities in early abstinent alcoholics are closely associated with alterations in thrombopoietin and erythropoietin serum profiles. Thrombosis and Haemostasis, 82: 1422-1427, (1999).

24. Ehrenreich, H., Mangolz, A., Schmitt, M., Lieder, P., Völkel, W., Rüther, E., Poser, W.: OLITA - an alternative in the treatment of therapy-resistant chronic alcoholics. First evaluation of a new approach. European Archives of Psychiatry and Clinical Neuroscience, 247: 51-54, (1997).

25. Ehrenreich, H., Schuck, J., Stender, N., Pilz, J., Gefeller, O., Schilling, L., Poser, W., Kaw, S.:Endocrine and hemodynamic effects of stress versus systemic corticotropin releasing factor in alcoholics during early and medium term abstinence. Alcoholism, Clinical and Experimental Research, 21: 1285-1293, (1997).

26. Ehrenreich, H., tom Dieck, K., Gefeller, O., Kaw, S., Schilling, L., Poser, W., Rüther, E.: Sustained elevation of vasopressin plasma levels in healthy young men, but not in abstinent alcoholics, upon expectation of novelty. Psychoneuroendocrinology, 22: 13-24, (1997).