Bipolar In Turkey

Drug Administration Patterns: BP I outpatients in Istanbul E. Timuçin Oral, Nesrin Koçal, Evrim Erten Özden Arısoy, Aytül Hariri, Erhan Kurt Bakirkoy State Hospital for Psychiatric & Neurological Diseases, Rasit Tahsin Outpatient Mood Disoders Unit, Istanbul / Turkey Rasit Tahsin duygudurum merkezi

Please change your drug, this one can not control your cycling

Changing face of Psychiatry in Bakırköy

4 2

2

Population: 73 000 000

Area: 769 604 sq km

Urban pop: 66 %

Demographics 

Number of physicians: approx.

100 000



Number of hospital beds:



Total number of psychiatric beds:



Prevalence of any psychiatric disorder

180 797

–

Under age 18:

22.2 %

–

Over age 18:

17.2 %

6 000



Suicide rate:

3.85 / 100 000



# Psychiatrists:



# Child Psychiatrists:



# Psychologists:



# Social workers:

2 / 100.000



# Nurses:

4 / 100.000

2 / 100.000 0,2 / 100.000 4 / 100.000

Basic Issues 

Classification System:



Problems: – – – – – – –

DSM (ICD for official use)

Differential Diagnosis (Schizoaffective Disorder) Lack of Investigating Hypomania in Depressive Patients Co-morbidity of endemic thyroid problems in black sea region Over crowded wards and lack of qualified staff Lack of community psychiatry: accumulation of patients in certain treatment centers Unwillingly hospitalized patients (Stigmatization) Lack of regulatory criteria (laws?) for hospitalization

Treatment Issues Mania 

MS (Li, VPA, CBZ) + AP (FGA in acute settings)



40-50 % parenteral application (up to 90 % in first three days)



ECT: 18,6 % – 28,6 % in state hospitals, 8,4 % in university clinics – ECT is applied in modified form in all through the country since 2005.

Bipolar Depression 

MS (Li, LMT sometimes solely) + SSRI



ECT: 1-30 % (differ in clinics)

Mixed Episode 

Generally not seen as it is in the literature, DSM is used for research but softer criteria in clinical routine

Treatment Issues Long-term 

MS (Li / Li+VPA / Li+LMT) after II. episode (except family hx, severity)



SGAs rising (FGA is rare, depots are extremely rare)

Psychotherapy 

Not common, most non-structured training strategies – – – –

Giving NSI both to patients and relatives Giving NSI to patients Giving NSI to relatives Structured psychoeducation

Stigma   

Better than Western Countries (esp in unchanged social parts) Admittance is still low in rural areas. Extended families still give support despite higher stigmatization.

What should be done? 

The illness must be explained better



Restricted number of beds requires outpatient treatment with a close supervision of the patient and the family: Psychoeducation needs attention



Enough attention should be given to the prophylaxis of the illness

Rasit Tahsin duygudurum merkezi

Ord. Prof. Dr. Raşit Tahsin Tuğsavul

BP Treatment Guidelines of PAT • To review the existing literature and knowledge • To introduce the opinions of experts and clinical consensus judgements when knowledge is lacking or not enough • To create a setting for discussion and interaction of the Turkish psychiatrists • To try to standardize treatment strategies without “recipes” • To produce a qualified “Turkish reference”

Algorithm for “Maintenance Treatment” 2nd or more episodes

1st episode

Severity of the episode

Not taking MS

Taking MS

Quality of life Positive family history The choice of the patient

Cont. MS start acute episode

Start MS (Li)

Or Cont. MS

Decision: YES Decision: NO

Taper down MS and STOP

Full remission

Recurrence or partial/minimal response

Decision

Combine 2 MSs

Continue treatment Alternatives

Next step To determine • the feasibility of the algorithm • the effectiveness of the medication algorithms • the application of the algorithms in different clinical settings

Treatment practice guidelines US • American Psychiatric Association • Texas Medication Algorithm Project • Expert Consensus Guidelines Europe • European Algorithm Project • Cochrane Library reviews • British Association of Psychopharmacologist guidelines • National and local initiatives (Dutch, Turkish etc) Worldwide • World Federation of Societies of Biological Psychiatry

Europe-USA similarities in BPD • Equivalent epidemiological studies • Equivalent diagnostic studies • Equivalent perspectives, training of experts • Equivalent care when provided by psychiatric experts in BP care

Main differences in EU practice / US algorithms • Longer maintenance of antipsychotic(s) alone • Possibility of two APs (one for sedation-conventional? + one atypical) • No combination of anticonvulsants at this stage • Augmentation with Li in case of non-response (considered as a starter in resistant patients) • Progressive administration of Li for maintenance (prophylaxis) purpose in case of response

Combination Therapy The rule, not the exception 60 20.9%

50

18.2%

Number of Patients

17.1%

40 12.0% 12.0%

30

20

6.6%

6.6%

10

3.1% 1.9% 0.8%

0.8%

0

0

1

2

3

4

5

6

7

8

Total number of medications Post RM, et al. J Clin Psychiatry. 2003;64:680-690.

9

10

Combination treatment, rather than monotherapy, is prevalent in the treatment of subjects with bipolar disorder, probably due to the complex and phasic nature of the illness. Levine et al, Bipolar Disord. 2000 Jun;2(2):120-30

457 BP I Li 50% VPA 40% CBZ 11% 1/3 of all receiving APs; 2/3 of them traditional APs 50% were receiving concomitant ADs SSRI 50% Buproprion 25% Benzos 40% Mono

18%

we should strive to achieve rational, yet pragmatic, treatment guidelines & algorithms to minimize the risks, while maximizing the benefits of these combination treatments for patients with BPD Levine et al, Bipolar Disord. 2000 Jun;2(2):120-30

Background: Pilot Study for SKİP-TÜRK • Aim: search for illness characteristics & drug administration patterns in a naturalistic setting • Site: the greatest & oldest institute of the country / a specialized outpatient unit registering MD patients • Time span: starting from the spring of 2003 • Future Plan: obtained data will shed light on colloborative research & will test treatment approach of Turkish BP algorithm

YAŞAM BOYU İZLEM ÇİZELGESİ

TEDAVİ MANİ

~

..

=°

Anksiyolitik Antipsikotik Li VPA CBZ

Şiddetli Şiddetli Orta Ilımlı Orta Hafif

Li

EKT

EKT

.

+

duygudurum merkezi

.

EKT

● EKT Antidepresan

Rasit Tahsin

VPA

*************

X

25

Yaşam Olayı

Etki Derecesi

Hafif Ilımlı Orta Şiddetli Orta Şiddetli

YORUM

DEPRESYON

YAŞ

YIL 1977

+4

1980

1990

1999

1994

+4

Peşpeşe

Annesinin

Eşinin

düşükler

ölümü

ölümü

2000

2001

2002

2003

Population • 241 BP Type I patients out of 266 registered in 8 months • Registered & evaluated with a structured follow-up form, developed & computerized by the Mood Disorders Section of Turkish Psychiatric Association for the database project to be used country-wide (SKİPTÜRK)

Patients • BP Type I patients registered only • BP : 203 UPM : 38

(UPM min 4 episodes and min 5 years)

• Genetic load – MD amongst first degree relatives 51.3% – MD amongst second degree relatives 45%

Demographics • Sex – 61.4 % male – 38.6 % female

• Mean age

35.61 ± 10.7 (16-67)

• Marital status – single 33.2 % – married 51.5 % – divorced or separated 15.4 % marriage & divorce F>M

14 12

Number of patients

10 8 6 4 2 0 16

23 20

29 26

35 32

41 38

47 44

53 50

61 57

67

Age

Demographics • Social & economic status • • • •

99 (42%) are housewifes 55 (22.8%) unemployed (45 % because of illness) 20 (8.2 %) retired 67 (27.8 %) are employed or students

> 8 Sheeham Disability Scale (%)

BPD & psychosocial impairment 25 20 15

BPD (n=1167) Controls (n=1283)

***

*** ***

10 5 0

Work / school

p<0.001 vs control subjects

Social / leisure life

Family life

Calabrese et al 2003

Illness characteristics • The first episode of the illness – Mania – Depression

54.9 % 38 %

– Mixed – Hypomania

1.7 % 1.6 %

– Dysthymia 0.4 % – Unidentified 3.8 % • Mean age of onset 22.53 ± 7.42 (10-58) • Duration of illness 12.83 ± 9.52 (0-52)

40

30

20

10

0 10

14 12

18 16

22 20

26 24

30 28

Duration of illness

34 32

38 36

44 41

51

Drug administration patterns • Mean duration with a mood stabilizer 7.33 ± 6.0 (0-27) • 109 (45.2%) receiving either lithium or anticonvulsants – 71 (29.4%) lithium alone – 28 (11.6%) in combination with valproate.

• AP + MS 132 (54.8%), – 42 (17.4%) sedative antipsychotics (chlorpromazine or thioridazine) for inducing sleep. – 6 conventional drugs – 61 (25.2%) second generation antipsychotics. Olanzapine 12.4%

Treatment of BP Mania in Acute-Maintenance/Prevention Periods in an Inpatient Unit Acute Period Rezistance = im APs / EKT Dangerousness Cooperation = Li (and/or VPA) + AP Maintenance

Li and/or VPA

Prevention

Li and/or VPA / Other MS

Prescribed Mood Stabilizers No Li/AC Li

13 125

5,5 % 52,7 %

VPA CBZ

30 5

12,7 % 2,1 %

Li+VPA Li+CBZ

58 1

24,5 % 0,4 %

VPA+CBZ VPA+Lam

1 1

0,4 % 0,4 %

Li+Lam

3

1,3 %

Proportions of MS drugs in the U.S. (2001) • Divalproate

33.4%

• Olanzapine

16.1%

• Risperidone

11.3%

• Gabapentin

11.1%

• Lithium

8.8%

• Quetiapine

8.5%

• Lamotrigine

3.6%

• Topiramate

3.6%

• Carbamazepine

3.6%

Li

VPA

CBZ

Kings of Preventıon

Prescribed Antipsychotics No AP Chlorpromazine Tioridazine Zuclopenthixol Haloperidole Clozapin Olanzapine Risperidone Quetiapine Sulpiride Amisulpiride

125 40 3 2 2 4 30 10 3 17 1

52,7 16,9 1,3 0,8 0,8 1,7 12,7 4,2 1,3 7,2 0,4

Prescription of Novel & Conventional Antipsychotics in Turkey 80 70

76 76

71 67

63 62

60 50 40

25

30

15

20

28

33

19

10 0

Conventional 1997

1998

Novel 1999

2000

2001

2002

35

Novel Antipsychotics 18 16 14 12 10 8 6 4 2 0

1997

Clozapine

1998

Sulpride

1999

2000

Risperidone

2001

Olanzapine

2002

Quetiapine

114 (47,3 %) patients are not using APs or ADs and only followed by MSs. Of these patients who are receiving only MS No drug

6

5,3

Li mono

71

62,3

VPA mono

9

7,9

Li+VPA

27

23,7

Li+Cbz

1

0,9

80 of them (70,2%) are on monotherapy with either Li or VPA and 28 (24,6 %) on Li + VPA

Mood Stabilizers No MS Mono-MS Double-MS

13 160 64

5,5 % 67,5 % 27 %

Antidepressants No AD SSRI SNRI-NaSSA

222 10 5

No AP Novel AP Conventional

125 34 47

93,7 % 4,2 % 2,1 %

Antipsychotics 52,7 % 14,4 % 19,8 %

VPA

Li-AP

Recent records... • 320 patients registered in 10 months • 1591 patients visits • 15 hospitalizations ( 4.6 %) – 12 in manic episode – 3 in depressive episode – once in a month & mean duration is 20 days

Conclusion • 1/3 of the patients are on monotherapy. • MS alone are not found satisfactory by the psychiatrists as monotherapeutic agents • The application of guidelines and a structered follow-up method, in a specialized setting may be helpful to reduce the number of combination treatments and risks for relapse.

The( Happy?)End

The (Happy?)End