1. _____________________________________________________________ IRPB Congress 26th - 28th April 2015 --- Lisbon Giuseppe Tavormina, M.D. President of Psychiatric Studies Centre (Cen.Stu.Psi.) Senior Research Fellow of BCMHR in collab. with Univ of Cambridge Provaglio d’Iseo (Brescia), Italy The “G.T. – MSRS”: a new rating scale to diagnose mixed states.

2. Mood in a person who is eutimic is stable. In mood disorders, the mood “swings” between depression and euphoria/irritability and therefore there is the “unstable mood”. A depressive episode is in fact only one phase of a broader “bipolar spectrum of mood”, in which instability of the mood is the main component. Depression Mania/ipomania euthymia Introduction Tavormina G - Agius M : ”Psychiatria Danubina”, 2007

3. Bipolar Mixed states Depressive mixed states Dysphoric (mixed) mania

4. Clinical evaluations - (1) The disorders of the bipolar spectrum (including sub- threshold forms) are really very common, more so than normally considered, even if they are pathologies which are often underestimated or not diagnosed or mis-treated (Tavormina G, Agius M, 2007). The consequence of this inadequate diagnosis and treatment can lead to various issues of public health, with serious consequences including abuse of substances, business difficulties, suicidal risk, family massacres, rapes, etc. (Akiskal-Rihmer, 2009; Tavormina G, 2010; Tavormina G, 2013).

5. Clinical evaluations - (2) The dysphoric component of the mood (mixed states) is quite frequent within all the subtypes of the bipolar spectrum (approximatively 30% of all mood spectrum). (Tavormina G, 2010; Tavormina G, 2013).

6. Tavormina G: ”Psychiatria Danubina”, 2010

7. ”Melancholia as defined today is more closely aligned with the depressive and/or mixed phase of bipolar disorder. Given the high suicidality from many of these patients, the practice of treating them with antidepressant monotherapy needs re-evaluation". Hagop Akiskal, Conference: 'Melancholia: Beyond DSM, Beyond Neurotransmitters', May 2–4, 2006, Copenhagen, Denmark Akiskal's schema of bipolar subtypes (1)

8. Bipolar ½ : schizobipolar disorder Bipolar I : core manic-depressive illness Bipolar I½ : depression with protracted hypomania Bipolar II : depression with discrete spontaneous hypomanic episodes (Bipolar II, "sunny" bipolars - hypomanic periods (2-3 days) characterized by cheerfulness and jocularity, people- seeking, increased sexual drive and behavior, talkativeness and eloquence, confidence and optimism, disinhibition and carefree attitudes, reduced sleep need, eutonia and vitality, and over-involvement in new projects) Bipolar II½ : depression superimposed on cyclothymic temperament (Bipolar II½: Unstable, "darker" BP II : dysphoric, irritable hypomania superimposed upon an inter-episodic cyclothymic temperament ("roller-coaster" course often misinterpreted or misdiagnosed as borderline personality disorder). Often comorbid with panic disorder and social phobia, as well as, bulimia and borderline personality disorder) Bipolar III : depression with induced hypomania (i.e., hypomania occurring solely in association with antidepressant or other somatic treatment) Bipolar III½ : prominent mood swings occurring in the context of substance or alcohol use or abuse Bipolar IV : depression superimposed on a hyperthymic temperament (Bipolar IV : VERY DANGEROUS condition - Depression superimposed on a stable hyperthymic temperament: exuberant, articulate and jocular, overoptimistic and carefree, overconfident and boastful, high energy level, full of plans and activities,... with broad interests, over involved, uninhibited and risk-taking, and an habitual short sleeper. And suddenly slip into deep (often ) treatment-resistent depression. This is an extremely DANGEROUS condition because hyperthymic individuals are intolerant of any degree of depression, and certainly poorly tolerate the affective dysfunction associated with a depressive mixed state. Many mysteries about suicide, and suicides that one reads about in the newspaper [ie, "an extremely successful and happy person, who had everything, put the gun in his mouth“] may well belong to this category). Akiskal's schema of bipolar subtypes (2) Akiskal HS, Pinto O: The evolving bipolar spectrum: Prototypes I, II, III, IV. Psychiatr Clin North Am. 1999; 22:517-534

9. Bipolar ½ : schizobipolar disorder Bipolar I : core manic-depressive illness Bipolar I½ : depression with protracted hypomania Bipolar II : depression with discrete spontaneous hypomanic episodes (Bipolar II, "sunny" bipolars - hypomanic periods (2-3 days) characterized by cheerfulness and jocularity, people- seeking, increased sexual drive and behavior, talkativeness and eloquence, confidence and optimism, disinhibition and carefree attitudes, reduced sleep need, eutonia and vitality, and over-involvement in new projects) Bipolar II½ : depression superimposed on cyclothymic temperament (Bipolar II½: Unstable, "darker" BP II : dysphoric, irritable hypomania superimposed upon an inter-episodic cyclothymic temperament ("roller-coaster" course often misinterpreted or misdiagnosed as borderline personality disorder). Often comorbid with panic disorder and social phobia, as well as, bulimia and borderline personality disorder) Bipolar III : depression with induced hypomania (i.e., hypomania occurring solely in association with antidepressant or other somatic treatment) Bipolar III½ : prominent mood swings occurring in the context of substance or alcohol use or abuse Bipolar IV : depression superimposed on a hyperthymic temperament (Bipolar IV : VERY DANGEROUS condition - Depression superimposed on a stable hyperthymic temperament: exuberant, articulate and jocular, overoptimistic and carefree, overconfident and boastful, high energy level, full of plans and activities,... with broad interests, over involved, uninhibited and risk-taking, and an habitual short sleeper. And suddenly slip into deep (often ) treatment-resistent depression. This is an extremely DANGEROUS condition because hyperthymic individuals are intolerant of any degree of depression, and certainly poorly tolerate the affective dysfunction associated with a depressive mixed state. Many mysteries about suicide, and suicides that one reads about in the newspaper [ie, "an extremely successful and happy person, who had everything, put the gun in his mouth“] may well belong to this category). Akiskal's schema of bipolar – focus on mixed states Akiskal HS, Pinto O: The evolving bipolar spectrum: Prototypes I, II, III, IV. Psychiatr Clin North Am. 1999; 22:517-534

10. Acute mania 1 - Bipolar I (  dysphoric mania) 2 - Bipolar II (  rapid cycling bipolarity, mixed disphoria) 3 - Cyclothymia (  rapid cycling bipolarity) 4 - Irritable Cyclothymia (rapid cycling bipolarity) 5 - Mixed Dysphoria (depressive mixed state) 6 - Agitated Depression (  depressive mixed state ) 7 - Cyclothymic temperament (  Mixed Dysphoria, depressive mixed state, rapid cycling bipolarity, agitated depression, bipolar I-II ) 8 - Hyperthymic temperament (  Agitated Depression, Irritable Cyclothymia, bipolar II ) 9 - Depressive temperament (  brief rec. depr, agitated depression ) 10 - Brief recurrent depression (  dysthymia, major depressive episode, agitated depression) Unipolar Depression Tavormina G - Agius M : ”Psychiatria Danubina”, 2007 My schema for Bipolar Spectrum Disorders sub-types

11. Bipolar Spectrum Disorders sub-types: mixed states 1 - Bipolar I 2 - Bipolar II 3 - Cyclothymia 4 - Irritable Cyclothymia (rapid cycling bipolarity) 5 - Mixed Dysphoria 6 - Agitated Depression 7 - Cyclothymic temperament 8 - Hyperthymic temperament 9 - Depressive temperament 10 - Brief recurrent depression Unipolar Depression 4 (frequent shifts from one phase to the other without euthymia, irritability, insomnia,...) 5 (permanent overlap between sadness, irritability, grief, rashness, difficult concentration, migraine, colitis, insomnia,...) 6 (restlessness, gloomy thoughts, muscolar tenseness, migraine, colitis, insomnia,...) Acute mania

12. Symptoms of Mixed States : The symptoms to note carefully on diagnosing mixed states are the following (at least two of these to be present at the same time): - overlapping depressed mood and irritablity, - reduced ability to concentrate and mental overactivity, - high internal and muscular tension, gastritis, colitis, headaches, or other somatic symptoms (for ex.: increasing of eczema or psoriasis), - comorbidity with anxiety disorders (PAD, GAD, Social phobia, OCD), - insomnia (mainly fragmentary sleep and/or low quality of sleep), - disorders of appetite, - a sense of despair and suicidal ideation, - hyper / hypo-sexual activity, - substance abuse (alcohol and/or drugs), - antisocial behaviour. Tavormina G - Psychiatria Danubina, 2013

13. H. Akiskal (2005):

14. The co-presence of various types of somatisation symptoms, as well as the abuse of substances, should suggest indisputably the possibility of a "mixed state" of the bipolar spectrum. The abuse of substances (alcohol, cannabis, cocaine and cannabinoids, etc.) may in turn cause depression, dysphoria, anxiety, and the so-called "amotivational syndrome". The concomitant abuse of substances with the mood disorders can make such patients resistant to treatments and lead to a worse prognosis. Tavormina G - “Psychiatria Danubina”, 2012

15. What treatment ? (1) The Bipolar Spectrum Disorder treatment will require special care, so that appropriate drugs are given. The pharmacological treatment of the bipolar mood disorders consists in a combination therapy between mood-regulators (mainly: lithium, carbamazepine, valproate, gabapentin, oxcarbazepine, lamotrigine, topiramate, olanzapine, pipamperone) and antidepressants (mainly: SSRI, SNRI). Tavormina G - “Psychiatria Danubina”, 2011

16. What treatment ? (2) Never using the antidepressants alone and/or in combination with benzodiazepine, and never using long time the benzodiazepine, both in order to avoide an increase in instability and the development in patient of the diphoric-mixed states. Tavormina G - “Psychiatria Danubina”, 2011

17. What treatment ? (3) A correct maintenance therapy, however, assessed and chosen from case to case, based on the clinical picture should always include at least one or two/three mood stabilisers together with low doses of antidepressant (above all in maintenance therapy). Tavormina G - “Psychiatria Danubina”, 2013

18. Considerations… The difficulties for the clinicians to do a correct diagnosis of the mood disorders they are valuing, above all when mixed states are present, induce them to frequently prescribe antidepressants drugs alone or together with benzodiazepines (sometimes because the patients mainly focus their own symptoms on depressive uneasiness) …

19. Considerations… … and not to put emphasis on the increasing dysphoria following this inadequate treatment !

20. Project (1) For this reason, the presence of a new rating scale, mainly focused on mixed states symptoms, is crucial ! None of other actual rating scales for mood disorders, despite being very useful (the “Bech-Rafaelsen Mania Scale”; the “Manic-State Rating Scale, MSRS”; the “Mood Disorder Questionnaire, MDQ”; the “Young Mania Rating Scale, YMRS”), are specific to all typologies of symptoms of the mixed state disorders, and so are too generic (as the MDQ) or too specific only for mania and bipolar I or II (all the others).

21. Project (2) “G.T. Mixed States Rating Scales”, or “G.T. MSRS” Tavormina G - “Psychiatria Danubina”, 2014

22. Project (3) “G.T. Mixed States Rating Scales”, or “G.T. MSRS” Tavormina G - “Psychiatria Danubina”, 2014

23. Project (4) “G.T. Mixed States Rating Scales”, or “G.T. MSRS” Tavormina G - “Psychiatria Danubina”, 2014

24. Project (5) “G.T. Mixed States Rating Scales”, or “G.T. MSRS” Tavormina G - “Psychiatria Danubina”, 2014

25. Project (6) “G.T. Mixed States Rating Scales”, or “G.T. MSRS” The positive result following to “G.T. MSRS” will enable a diagnosis for mixed states sub-types of bipolar spectrum disorders: - the sub-groups n° 3,5,7 and 8 of the Akiskal’s scheme, - and the sub-types cyclothymia, irritable cyclothymia, rapid cycling bipolarity, mixed dysphoria, agitated depression and cyclothymic temperament of the Tavormina’s scheme. Tavormina G - “Psychiatria Danubina”, 2014

26. Project (7) “G.T. Mixed States Rating Scales”, or “G.T. MSRS” The clinician will need of special care to do the correct sub-diagnosis of sub- groups of mixed state.

27. Conclusions (1) The consequences of the lack of recognition and treatment of a mood disorder mixed states can be: - higher risk of suicide, - reduction in the expectation and/or the quality of life (personal, family and work), - increased loss of working days, - increased use of health care resources, including for concurrent diseases, - and finally the mood can become chronic and the clinical picture can worsten.

28. Conclusions (2) The clinician needs to have all the modalities to enable him to make a correct diagnosis wherever possible and a correct pharmacological treatment. For this reason the “G.T. MSRS” has been created: to improve the clinical activity of psychiatrists.

29. A Guide on Mood Disorders for Doctors :

30. A short Guide on Mood Disorders for population: Italian version… www.sardini.it

31. A short Guide on Mood Disorders for population: … and English version www.sardini.it