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    Using data of patients with various anxiety and depressive disorders from the WHO Collaborative Study on psychological problems in general health care [ 66 ], Barkow et al. The authors concluded that patients suffering from MADD are either only transiently affected or in a prodromal or residual state of a syndromal affective disorder.

    It should be noted, however, that the 1-year recovery rates reported by Barkow et al.

    Similar observations were also published by Spijker et al. Using taxometric methods, Schmidt et al.

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    Their results also support previous findings according to which MADD may be predictive of subsequent syndromal anxiety and depressive disorders [e. In a survey of more than 21, patients who attended primary care for any reason, Balestrieri et al.

    The results dispute the hypothesis that co-morbid, subsyndromal anxiety and depression should be viewed as a state of partial remission of a previous syndromal disorder.

    Based on representative population survey data of respondents in Great Britain, Das Munshi et al. Using latent class analysis, the authors found considerable overlap between patients with MADD, those with depression and co-morbid anxiety, and those with anxiety and co-morbid depression, based on the presence of negative affect. The authors interpreted their results as challenging the notion of these conditions as having distinct phenomenologies.

    Although Hettema et al. Moreover, MADD was found to be significantly associated with childhood adversity, poor parenting, lifetime traumas, recent life events, high neuroticism, co-morbid substance-use disorders, and familial aggregation. The authors conclude that MADD is a commonly occurring, identifiable, syndromal subtype that should be considered for inclusion in future nosological systems.

    In a study performed in Germany, data from a random sample comprising However, the quality of these diagnoses was not scrutinized, so that it cannot be excluded that in many cases MADD was diagnosed although the patients fulfilled the full criteria for both syndromal depression and an anxiety disorder.

    Moreover, some studies have excluded patients with a lifetime history of other anxiety or depressive disorders [ 67 , 72 ], while others have not [e. Nevertheless, there is also heterogeneity between some studies using the criteria from the same classification system. While the authors conclude that a diagnostic category of MADD is not helpful and may even encourage cursory evaluation of patients rather than motivate physicians to reliably distinguish between anxiety and depression, their findings may also be interpreted in favor of a better operationalization of the diagnostic criteria of MADD, particularly for use in primary care.

    It should also be noted that the true prevalence of MADD is likely underestimated by community-based studies since affected individuals frequently present in primary care with somatic, rather than psychological, complaints [ 78 ].

    Nosological issues There is an ongoing debate as to whether a diagnostic category of MADD is required for appropriately classifying patients with co-morbid, subthreshold anxiety and depression. While some researchers prefer a simultaneous classification of subthreshold anxiety disorder and subthreshold depression [e. The proposal to code subthreshold anxiety and subthreshold depression separately implies the notion that the patient is suffering from 2 independent, readily distinguishable, and thus separately codable disorders.

    It should be noted, though, that throughout the history of psychiatric classification neurotic depression and anxiety were perceived to be closely related concepts [ 13 , 15 ] that were placed in 2 different classes of disorders only in DSM-III. As shown above, both phenomenological and neurobiological evidence suggest that such a strict separation may not be appropriate as anxiety and depression may be better explained as the extremes of a continuum characterized by non-specific distress or negative affect.

    Moreover, it is worth mentioning that current classification systems do not even include dedicated diagnostic categories for either subthreshold depression or anxiety. As regards the second proposal, to classify patients with co-morbid, subthreshold depression and anxiety as either suffering from anxiety or depressive disorder, epidemiological studies indicate that approximately half of the patients with MADD develop a syndromal psychiatric disorder within about a year [ 27 , 72 ].

    Therefore, it has been argued that if MADD is actually a prodromal stage of another psychiatric disorder, it should be classified in accordance with this disorder, not as an independent diagnostic concept [ 79 ]. Batelaan et al. Indeed, Tyler [ 29 ] has already pointed out that the discussion about the usefulness of MADD as a diagnostic category has mainly be focused on coexisting, subsyndromal presentations.

    Along the same line, a double threshold concept has been suggested which defines one threshold for mental disorder and a second lower threshold for mental health [ 80 ]. The resulting between-threshold zone of subthreshold mental illness could be useful in applying treatment according to disease severity, optimizing cost-effectiveness, and controlling the burden to the healthcare system [ 81 ].

    A study focusing on the consequences of illness on distress as well as on social, occupational, and psychological functioning showed, however, that the symptom profiles of patients with MADD were easily distinguishable from those of patients with MDD but were similar to those of patients with GAD from which they differed significantly only in more severe depressed mood and less severe somatic symptoms of anxiety [ 82 ].

    Diagnosis determines treatment Although anxiety and depression symptoms in MADD are subsyndromal by definition, they may nevertheless cause similar levels of distress and disability as those observed in patients with a syndromal diagnosis [e. Epidemiological data and reports from clinical practice suggest, however, that patients suffering from subsyndromal anxiety or depressive symptoms are often underrecognized and, consequently, undertreated [ 64 , 91 , 92 ].

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    We would therefore like to emphasize the importance of an appropriate diagnostic category in order to guide appropriate treatment. For example, in a study published by Kunik et al. This may be another important factor contributing to the underrecognition of MADD in primary care. Since MADD is associated with significant disability and impaired health-related quality of life, but in most cases is not a life-threatening condition, treatment should focus on the restoration of daily living skills and social functioning as well as on the prevention of an exacerbation to a potentially more serious psychiatric disorder, and should include only very limited risk.

    Of note, the use of drugs whose bothersome and partly disabling adverse effects, such as anticholinergic reactions, headache, sedation, gastrointestinal complaints, somnolence, weight gain, sexual dysfunction, or even anxiety and co-morbid insomnia, could aggravate the symptoms they were prescribed to treat, should be avoided. Co-morbid anxiety and depression have been shown to respond favorably to cognitive behavioral therapy [ 95 , 96 ].

    However, psychotherapy is often no viable option, due to lack of places on treatment programs. Therefore drugs that provide symptom alleviation at minimal risk are particularly important. Up to now, there are only few randomized treatment studies for MADD.

    This is in contrast to the substantial diagnostic overlap among all anxiety disorders. Moreover, there is no evidence for a differential indication of certain treatments for the different anxiety disorders. Instead, it has been shown that the effect sizes obtained with medications for the different anxiety disorders are very similar [ 97 ].

    Our concern is with patients who suffer profoundly from distress and disability and whose symptoms, when considered in their entirety, clearly possess pathological significance.

    Denying such patients an appropriate diagnosis could well imply to withhold the required treatment as well. Among the non-remitting patients a substantial proportion was found to progress to a syndromal depressive or anxiety disorder or to another syndromal psychiatric diagnosis [ 27 , 72 ]. Lamentably, factors allowing to reliably predict the course of MADD, and to differentiate between patients who are likely to remit spontaneously and those who are at a substantial risk of progression to a syndromal affective disorder, are yet to be identified [ 74 ].

    Since individuals with subthreshold affective disorders may experience similar levels of distress and disability as patients with a syndromal diagnosis, patients with MADD also exhibit similar social and occupational dysfunction [ 90 ].

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    As shown for minor depression [ 98 ], subthreshold disorders like MADD are associated with similar indirect, non-medical costs e. The recognition of MADD as a condition requiring treatment may thus result in increased costs for healthcare utilization, but may nevertheless be cost-effective from a societal perspective.

    In day-to-day clinical practice, particularly in primary care, physicians diagnose and treat large numbers of patients who present with comparatively trivial, self-limiting disorders.

    Of course, treatment of the common cold appears to be perfectly justified both from a clinical and from an economic perspective, since a patients suffer, b there is a certain risk of much more severe and difficult to treat complications and exacerbations, and c secondary costs, resulting from disability, may be reduced by an acceleration of recovery. We have never heard of any criticism of common cold treatment founded in the conviction that a diagnosis of the disorder could lead to unjustified medicalization and stigmatization of millions of individuals who suffer from minor, self-limiting symptoms.

    One thing that somatic and psychiatric disorders have in common is that patients suffer. Since they do, physicians should attempt to assign a matching diagnosis and to initiate appropriate treatment. Rather than to lament the potential stigmatization through mental illness, and denying an appropriate diagnosis, the medical community should better work toward an end of the stigmatization of mental illness in general. The inclusion of the diagnostic category of MADD into our classification systems will help patients to gain access to appropriate treatment early.

    At least, successful treatment will reduce their suffering, even if the symptoms would otherwise have subsided after some time untreated. Moreover, there is also a fair chance that early treatment will prevent an exacerbation to a more serious condition. This is why we think that a diagnostic category of MADD is both justified and helpful in clinical practice. Compliance with ethical standards Conflict of interest Prof.

    Among atypical antipsychotics, risperidone and olanzapine have been shown to reduce both the positive and the negative symptoms significantly of schizophrenia [ 2 ], and are also more effective than conventional antipsychotic drugs [ 3 ]. Risperidone and olanzapine exploit multiple actions on serotonin and dopamine which resulted in improved adherence by minimising the side effects of extrapyramidal [ 4 ] [ 5 ].

    One way of measuring the positive symptoms, the negative symptoms, and the general symptoms in schizophrenic patients is by using Positive and Negative Syndrome Scale PANSS. The measurement of the scores of PANSS has been proven to be sensitive and specific about the use of pharmacology from the assessment of the positive symptoms and the negative symptoms in schizophrenic patients [ 6 ].

    Several studies have been conducted to compare the effectiveness of olanzapine and risperidone using the scores of PANSS. Conley et al. In addition, patients treated with olanzapine appear to maintain a better response than patients treated with risperidone [ 7 ].

    This contrasts with previous findings by Tran et al. On the other hand, the positive scale and the total score between the two groups were found to be comparable [ 8 ]. Similarly, Shah et al. To our best knowledge, there is no previous study which limits participants only to patients with a specific gender. Therefore, this study aimed to measure differences in the scores of PANSS on the use of olanzapine and risperidone limited to male with schizophrenia who were hospitalised with a fixed dose.

    The inpatient method was chosen because this method could easily control the physical activity and lifestyle of the participants so that the results would have a more valid value. The reason for selecting male participants was because male schizophrenic patients tend to have negative symptoms, a worse pre-morbid history, and a greater likelihood of having deficit syndromes and worse prognosis than female schizophrenic patients [ 11 ].

    Methods The research design was a quasi-experiment with pre-test and post-test, between the olanzapine group and the risperidone group in the period of June-September The drop-out criteria used was an intention to treat analysis in which if there was a drop -out subject, the subject would still be included for the analysis in the last week with the data used was the data recorded in the last week before the subject dropped-out [ 12 ].

    The subject used was determined by non -probability sampling known as the consecutive sampling [ 13 ]. Subjects who met the criteria were required to sign an informed consent after being briefed about the study.

    According to that, this study recruited subjects of 68 male patients with schizophrenia who were hospitalised in the acute phase of treatment at the Mental Hospital Prof. Ildrem, North Sumatra, Indonesia. These participants were divided into two groups based on simple randomisation consisting of 34 patients treated with olanzapine treatment and 34 patients treated with risperidone treatment. If the subject encountered the side effects of extrapyramidal symptoms during the treatment, the subject would be given anticholinergic i.

    It was rated from 1 not present to 7 extremely severe with the score ranged from 5 to 35 [ 17 ].

    The exclusion criteria consisted of having general medical disorders or other comorbidities, history of substance use except caffeine and nicotine , and hypersensitivity or unresponsive to olanzapine dan risperidone.