The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An Algorithm for Generalized Anxiety Disorder.

The Psychopharmacology Algorithm Project at the Harvard South Shore Program (PAPHSS) published algorithms for bipolar depression in 1999 and 2010. Developments over the past 9years suggest that another update is needed. The 2010 algorithm and associated references were reevaluated. A literature search was conducted on PubMed for recent studies and review articles to see what changes in the recommendations were justified. Exceptions to the main algorithm for special patient populations, including those with attention-deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), substance use disorders, anxiety disorders, and women of childbearing potential, and those with common medical comorbidities were considered. Electroconvulsive therapy (ECT) is still the first-line option for patients in need of urgent treatment. Five medications are recommended for early usage in acute bipolar depression, singly or in combinations when monotherapy fails, the order to be determined by considerations such as side effect vulnerability and patient preference. The five are lamotrigine, lurasidone, lithium, quetiapine, and cariprazine. After trials of these, possible options include antidepressants (bupropion and selective serotonin reuptake inhibitors are preferred) or valproate (very small evidence-base). In bipolar II depression, the support for antidepressants is a little stronger but depression with mixed features and rapid cycling would usually lead to further postponement of antidepressants. Olanzapine+fluoxetine, though Food and Drug Administration (FDA) approved for bipolar depression, is not considered until beyond this point, due to metabolic side effects. The algorithm concludes with a table of other possible treatments that have some evidence. This revision incorporates the latest FDA-approved treatments (lurasidone and cariprazine) and important new studies and organizes the evidence systematically.

The psychopharmacology algorithm project at the Harvard South Shore Program: An algorithm for adults with obsessive-compulsive disorder

Back to table of contents Previous article Next article Communications and UpdatesFull AccessAddressing Sleep Impairment in Treatment Guidelines for PTSDAna Nectara Ticlea, M.D., Laura A. Bajor, D.O., and David N. Osser, M.D.Ana Nectara TicleaSearch for more papers by this author, M.D., Laura A. BajorSearch for more papers by this author, D.O., and David N. OsserSearch for more papers by this author, M.D.Published Online:1 Sep 2013https://doi.org/10.1176/appi.ajp.2013.13050641AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We reviewed Dr. Germain’s article (1) in the April issue with much interest. We would like to kindly correct Dr. Germain’s statement that no treatment guidelines have proposed that the initial treatment for posttraumatic stress disorder (PTSD) should focus on sleep impairment. The PTSD algorithm of the Psychopharmacology Algorithm Project at the Harvard South Shore Program (2), published in 2011, provides treatment guidelines that support exactly the idea that sleep evaluation and treatment should be the first step in assessing and treating PTSD. Notably, the first reference in the Psychopharmacology Algorithm Project article is to previous research by Dr. Germain and colleagues (3).From a psychopharmacological perspective, the availability of prazosin (4), which has demonstrated a much larger effect size than the selective serotonin reuptake inhibitors (SSRIs), a greater tolerability profile, and a shorter time to response, makes this approach possible. Many experts continue to promote SSRIs as a first-line treatment for this disorder, but the evidence—despite U.S. Food and Drug Administration approval of two SSRIs—remains not at all impressive (5, 6). SSRIs have a small effect size in ameliorating the range of PTSD symptoms, and they frequently exacerbate insomnia and nightmares. Furthermore, they often produce disabling sexual side effects.For many patients, sleep fragmentation may exacerbate daytime PTSD symptoms (hypervigilance, avoidance, and reexperiencing), and these symptoms may improve when sleep improves (7). The importance of sleep in regulating trauma-related memories and emotions has significant clinical implications, suggesting that prioritized interventions to correct sleep disturbances may facilitate the psychotherapeutic processing of traumatic events.From Harvard Medical School at the VA Boston Healthcare System, Brockton Division, Brockton, Mass.The authors report no financial relationships with commercial interests.References1 Germain A: Sleep disturbances as the hallmark of PTSD: where are we now? Am J Psychiatry 2013; 170:372–382Link, Google Scholar2 Bajor LA, Ticlea AN, Osser DN: The Psychopharmacology Algorithm Project at the Harvard South Shore Program: an update on posttraumatic stress disorder. Harv Rev Psychiatry 2011; 19:240–258Crossref, Medline, Google Scholar3 Germain A, Buysse DJ, Nofzinger E: Sleep-specific mechanisms underlying posttraumatic stress disorder: integrative review and neurobiological hypotheses. Sleep Med Rev 2008; 12:185–195Crossref, Medline, Google Scholar4 Raskind MA, Peterson K, Williams T, Hoff DJ, Hart K, Holmes H, Homas D, Hill J, Daniels C, Calohan J, Millard SP, Rohde K, O'Connell J, Pritzl D, Feiszli K, Petrie EC, Gross C, Mayer CL, Freed MC, Engel C, Peskind ER: A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry 2013; 170:1003–1010 (Epub ahead of print: Jul 12, 2013)Link, Google Scholar5 National Collaborating Centre for Mental Health: Posttraumatic Stress Disorder: The Management of PTSD in Adults and Children in Primary and Secondary Care. London; Leicester, UK, Gaskell and the British Psychological Society, 2005Google Scholar6 Committee on Treatment of Posttraumatic Stress Disorder, Institute of Medicine: Treatment of posttraumatic stress disorder: an assessment of the evidence. Washington, DC, National Academies Press, 2008Google Scholar7 Thompson CE, Taylor FB, McFall ME, Barnes RF, Raskind MA: Nonnightmare distressed awakenings in veterans with posttraumatic stress disorder: response to prazosin. J Trauma Stress 2008; 21:417–420Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited bySleep, circadian system and traumatic stress28 September 2021 | European Journal of Psychotraumatology, Vol. 12, No. 1Traumatic stress and the circadian system: neurobiology, timing and treatment of posttraumatic chronodisruption27 November 2020 | European Journal of Psychotraumatology, Vol. 11, No. 1Multilevel Interactions of Stress and Circadian System: Implications for Traumatic Stress28 January 2020 | Frontiers in Psychiatry, Vol. 10Potential pleiotropic beneficial effects of adjuvant melatonergic treatment in posttraumatic stress disorder29 April 2016 | Journal of Pineal Research, Vol. 61, No. 1Current Opinion in Psychiatry, Vol. 27, No. 5 Volume 170Issue 9 September 2013Pages 1059-1059 Metrics PDF download History Accepted 1 June 2013 Published online 1 September 2013 Published in print 1 September 2013

Background: The Psychopharmacology Algorithm Project at the Harvard South Shore Program (PAPHSS) has published evidence-supported algorithms for the pharmacological treatment of major depressive disorder with psychotic features (psychotic depression) in 1998 and 2008. This article is an update for the 2008 algorithm. Method: Using similar methodology as with the 2008 update, PubMed and EMBASE searches were conducted to identity relevant literature in the English language from November 2007 through July 2012. Articles were evaluated for quality of the data and for whether they provided additional evidence support for previous recommendations or prompted changes to the prior algorithm. Results: Minor changes were made to the algorithm: most prior recommendations were upheld. The most effective treatment for hospitalized, severe psychotic depression patients remains electroconvulsive therapy (ECT). The combination of an antidepressant (tricyclic [TCA], selective serotonin reuptake inhibitor [SSRI], or serotonin-norepinephrine reuptake inhibitor [SNRI]) plus an antipsychotic continues to be the preferred pharmacological modality when ECT is an unavailable/deferred option. Since the last update, new evidence tends to support using venlafaxine ER, a SNRI, as the first choice antidepressant. Regarding the antipsychotic, both olanzapine and quetiapine have new data demonstrating efficacy. Nevertheless, it is suggested that it may be reasonable to try other atypical antipsychotics with more benign safety profiles (e.g. ziprasidone, aripiprazole) as the first choice antipsychotic. New data also suggest at least four months of maintenance therapy is effective. If the first antidepressant-antipsychotic combination produces an unsatisfactory outcome, and ECT is still not acceptable or appropriate, the second pharmacotherapy trial can be with a change in the antidepressant, as was recommended in the 2008 algorithm. After two trials of combination therapy have failed (and, again, ECT is not an option), the algorithm continues to recommend augmentation with lithium. Limited evidence also suggests consideration of a switch to clozapine monotherapy. Augmentation with methylphenidate is a newly mentioned possible option based on very small evidence. When combination therapy is deferred, evidence suggests monotherapy with a TCA may be more effective than an SNRI or SSRI. However, safety issues and possible increased risk of psychosis exacerbation are unfavorable factors for TCA monotherapy. ECT or addition of an antipsychotic should be reconsidered if antidepressant monotherapy failed. Conclusion: This heuristic further refines the previous PAPHSS analysis of the available evidence for pharmacological treatment of psychotic depression. The validity of the conclusions is limited by the quality and quantity of the literature available: the number of head-to-head prospective trials in psychotic depression is still relatively small. However, this algorithm m

Participants of expert group on CPG for Obsessive Compulsive Disorder Adarsh Tripathi, Om Prakash Singh, Paramjeet Singh, Tushar Jagawat, M, Aleem Siddiqui, K.K. Verma, D.M. Mathur INTRODUCTION Obsessive-compulsive disorder (OCD) is a common psychiatric illness with lifetime prevalence of 1-3% [1]. It is the fourth-most common psychiatric illness and a leading cause of disability. OCD is associated with significant impairment in functioning, quality of life and disability. If untreated, OCD is a chronic illness with a waxing and waning of symptoms. A recent meta-analysis of long-term naturalistic prospective studies demonstrated that nearly a half of patients experience remission with much higher rates of remission in Indian patients compared to those in the west [2]. Early diagnosis and appropriate treatment may improve outcomes. Despite OCD being a common mental illness, most seek treatment after several years of suffering. Those who suffer from OCD tend to be secretive about their symptoms and suffer from shame and embarrassment. Less than a third of OCD sufferers receive appropriate pharmacotherapy and even less receive evidence-based psychotherapy. Symptoms The hallmarks of OCD are presence of obsessions and compulsions. Obsessions are repetitive, unwanted, intrusive thoughts, images or urges that are mostly ego-dystonic and cause severe distress or anxiety. Compulsions (or rituals) are repetitive behaviours or mental acts that are performed in response to an obsession to reduce anxiety/distress or prevent a dreaded consequence. Obsessions and compulsions are time consuming, distressing and are often resisted unsuccessfully. Clinical manifestations of OCD are remarkably similar across cultures and geographic locations. Common obsessions and compulsions and symptom dimensions identified through factor-analytical studies are shown in Table 1.Table 1: Common symptoms of OCDDiagnosis Many people experience intrusive thoughts and exhibit repetitive behaviours. A diagnosis of OCD is made only if symptoms are time consuming (e.g., more than an hour per day), distressing or cause significant interference in functioning. This is reflected in DSM-5 diagnosis of OCD and in the upcoming ICD-11 [3]. The ICD-11 criteria for OCD are likely to be very similar to the DSM-5 criteria [34]. The ICD-11 may include an insight specifier along the same lines as DSM-5. There are sweeping changes to the description of OCD in the proposed ICD-11. Duration criteria and subtyping of OCD may be removed in the revision for lack of evidence and clinical relevance. In ICD-10, a diagnosis of OCD was discouraged in the presence of schizophrenia, tic disorder or depression. This criterion too may be removed paving the way to make a diagnosis of OCD even in the presence of these comorbid disorders. Another major change to the diagnosis of OCD is creation of OCD and related disorders in DSM-5 (and in the ICD-11) and exit from the group of anxiety disorders. Many disorders are included in this group: body dysmorphic disorder (BDD), trichotillomania (TTM), skin picking disorder, hoarding disorder, substance/medication-Induced obsessive-compulsive and related disorder and obsessive-compulsive and related disorder due to another medical condition. In the upcoming ICD-11, few other conditions find a place in this group that include tic disorders, hypochondriasis and olfactory reference syndrome. All these disorders are grouped together based on shared clinical features (e.g., repetitive behaviours), comorbidity patterns, familiality, neuropsychological deficits, treatment response and importantly shared brain circuitry abnormalities. Hoarding disorder which may not share many features with OCD is grouped along with OCD because of historical association with OCD and obsessive-compulsive personality disorder. Comorbidity OCD is often comorbid with other psychiatric disorders. It is important to assess all patients with OCD for associated psychiatric comorbidity since they may have an effect on treatment outcome if left untreated. Depression and anxiety disorders are present in over a half of patients seeking treatment for OCD. Common comorbid disorders are listed in Table 2. Those with early onset OCD, in particular those with onset in childhood have high rates of attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and tic disorders.Table 2: Comorbid disorders in OCDBipolar disorder, in particular type 2, is reported to be not uncommon in OCD [5]. Similarly, OCD is not uncommon in those with primary diagnosis of bipolar disorder [67]. OCD when comorbid with bipolar disorder tends to run an episodic course [8] with worsening of symptoms in depressive phases and improvement in hypomania/ mania phases. It is important to recognise OCD-bipolar comorbidity because of treatment implications. The specific serotonin-reuptake inhibitors (SSRIs) traditionally used to treat OCD may induce switch to mania or rapid cycling course. Obsessive-compulsive symptoms and OCD are not uncommon in schizophrenia. Nearly a third of schizophrenia patients report OC symptoms or OCD. Presence of OCD may have a negative effect on the long-term course of schizophrenia. Therefore treatment of OCD with SSRIs and cognitive-behavior therapy (CBT)/behavior therapy (BT) may have to be considered although there is not much of systematic evidence supporting their efficacy in treatment of OCD in schizophrenia. COMMON INGREDIENTS OF MANAGEMENT PLAN Common ingredients of managing OCD include the following: Detailed assessment of symptoms and comorbid patterns including suicidal behaviours either by unstructured clinical interview alone or supplementation with structured assessments. Decision on setting for treatment (outpatient vs. inpatient care depending upon the severity, treatment resistance etc.) Detailed psychoeducation of the patient and family member (s) about OCD, its course and treatment options including duration of treatment. Choice of treatment: drugs vs. CBT vs. combination In the Indian context, SSRIs are first-line treatments preferred over CBT because of feasibility, affordability and limited number of trained therapists. CBT may be considered if SSRIs alone are not beneficial. Discussion on side-effects of drugs; in women risks vs. benefits of drugs during pregnancy and in the post-partum period Follow-up plan after initiating treatment ASSESSMENT AND EVALUATION In routine clinical practice, use of structured / semistructured interviews and rating scales may not be necessary. They are optional. However, they may be used when the clinician needs supplementary information. A list of useful instruments in the assessment of OCD is provided in Table 3.Table 3: Commonly used instruments to assess OCD (optional)The Yale-Brown Obsessive-Compulsive Scale (YBOCS) is the most widely used severity rating scale for OCD in both adults [9] and children [10] and is considered a gold standard instrument to measure severity of OCD. It is a 10-item observer-rating scale, also available as self-rated instrument. It measures the overall severity of obsessive-compulsive symptoms for the preceding week. The YBOCS is a global measure of symptoms and does not provide severity of individual symptom dimensions. A total score of ≥ 16 is considered to be indicative of clinically significant OCD. The YBOCS severity scale also has an associated symptom check list of 15 categories of obsessions and compulsions including miscellaneous symptoms. The checklist elicits both current (1 month) and past symptoms. On the YBOCS item-11 insight scale, the insight is graded as follows: 0 = excellent (fully rational thinking), 1= good insight (readily acknowledges absurdity or excessiveness but has some lingering doubts), 2 = fair insight (reluctantly admits absurdity, but waivers; has some unrealistic fear but no fixed conviction), 3 = poor insight (overvalued ideas; maintains they are not unreasonable or excessive, but acknowledges validity of contrary evidence), and 4 = lack of insight (delusional). A higher score on the Y–BOCS item-11 indicates poorer insight. FORMULATING A TREATMENT PLAN Formulating a treatment begins with correct diagnosis of OCD as per the DSM or ICD classificatory systems. When feasible a structured clinical interview is recommended to obtain a comprehensive account of patient's problems. Once a diagnosis is established, a detailed assessment of symptom profile is mandatory. Family members often accommodate patient's rituals and contribute to poor outcome. In most severely ill patients, an elaborate family assessment may be needed. Once assessment is complete, short-term and long-term goals of treatment have to be established. Enhancing treatment adherence is a vital aspect of formulating a treatment plan. It is important to educate patients about lag in the onset of action of drugs and that improvement may occur over several months of continuous treatment. Brief education about basic principles of psychotherapy should be explained if psychotherapy is being planned. Essentials of formulating a treatment plan are summarized in Table 4. All patients and their immediate family members should be provided psychoeducation about OCD (Table 5).Table 4: Essentials of formulating a treatment planTable 5: Components of psychoeducationCHOICE OF TREATMENT SETTINGS In the Indian scenario, treatment is either on an outpatient or an inpatient basis. Outpatient treatment is usually sufficient for most OCD patients who are mild to moderately ill and for those who are likely to be adherent to treatment. Patients may be followed-up at periodic intervals, initially once in a month or two and subsequently at longer intervals depending upon the response to treatment and tolerability and side-effects. Hospital treatment may be considered for those who are at high suicide risk, dangerous to self or others, and intolerant to side-effects. Many severely ill and treatment-resistant patients may require prolonged (2-3 months) hospitalization for intensive treatment with CBT and for rationalization of pharmacotherapy. Inpatient care may also be required for severe depression, mania or psychosis that may be comorbid with OCD. Admission in rehabilitation services may be necessary for some patients who may not have benefited from standard treatments including inpatient care. PHARMACOLOGICAL TREATMENT The clinical practice guideline is framed based on a review of relevant scientific literature. As a first step, we framed relevant questions which arise in the minds of the practitioner while treating a patient suffering from OCD. A literature search was conducted in PubMed to answer these questions. We also reviewed the existing guidelines on treatment of OCD [11121314]. After a thorough literature review, the treatment strategies were rated based on the Strength of Recommendation Taxonomy (SORT) [15]. Consistent evidence from multiple randomized controlled trials (RCT) constitutes the highest level of evidence for a recommendation. However, the external validity of RCTs has been questioned due to the rigid protocols in undertaking the studies. A practitioner may make a clinical decision based on the available evidence considering other relevant factors that influence the decision making process. A non-exhaustive list of these factors might include psychiatric and other medical comorbidities, previous treatment trials, affordability, accessibility, hypersensitivity, side-effect profile, patients' values etc. RELEVANT CLINICAL ISSUES First-line pharmacological treatment for OCD Meta-analyses of RCTs show that selective-serotonin reuptake inhibitors (SSRIs) are significantly more effective than placebo in the treatment of OCD [16]. SSRIs are associated with many adverse effects but are usually well tolerated. The only other medication which has shown to be consistently effective in OCD is the serotoninergic tricyclic antidepressant clomipramine. Clomipramine has been found to be significantly more effective than placebo in multiple RCTs and meta-analysis of RCTs [16]. Network meta-analysis comparing the efficacy of clomipramine vs. SSRIs failed to find any efficacy advantage over SSRIs [16]. Most head-to-head comparison trials have not found any significant difference between the efficacy of clomipramine and SSRIs [17]. Further, meta-analyses and individual RCTs have found that the tolerability of clomipramine is worse than that of SSRIs [1317]. The anticholinergic, cardiac and neurological side effects of clomipramine may be problematic in this regard. CONSIDERING THE CONSISTENT EFFICACY AND BETTER TOLERABILITY, GUIDELINES RECOMMEND SSRIs AS FIRST LINE TREATMENT FOR OCD (TABLE 6). Choice of SSRITable 6: Medications recommended as monotherapy in OCDMeta-analyses comparing the different SSRIs [16] and direct head-to-head comparisons [1718] have not shown superiority of any one SSRI over the other. SSRIs differ to some extent in their propensity to cause certain adverse effects and drug interactions. However, there is no unequivocal evidence to suggest that these differences may be clinically meaningful. Recently, concerns have been raised regarding cardiac adverse effects with high dose of citalopram, which is commonly used in OCD. Hence, high-dose citalopram may be used with caution in those with risk for arrhythmias. THE PRACTITIONER IS RECOMMENDED TO CHOOSE AN SSRI FOR AN INDIVIDUAL PATIENT BASED ON FACTORS SUCH AS PREVIOUS RESPONSE, COMORBIDITY, TOLERABILITY, ACCEPTABILITY, ADVERSE EFFECTS, COST AND DRUG INTERACTIONS. Dose of SSRI It is generally recommended that OCD be treated with a higher dose of SSRI than that used in depression (Table 5). A meta-analysis of fixed-dose comparison studies have found a greater efficacy with higher doses of SSRI (60-80 mg fluoxetine equivalent) compared to medium (40-50 mg fluoxetine equivalent) and low doses (20-30 mg fluoxetine equivalent) [19]. However, all three dose ranges were significantly more effective than placebo. The increased efficacy comes at the cost of poor tolerability as evidenced by increased dropouts due to adverse effects [19]. A review of individual fixed-dose comparison studies found that the dose-response relationship is more evident for escitalopram, fluoxetine and paroxetine, while it is less clear-cut for citalopram and sertraline [17]. Clomipramine has not been tested in such fixed dose comparison studies. However, most studies have employed a flexible dosing at 150-250 mg [17]. It should be remembered that there is likely to be inter-individual differences in pharmacokinetic profile of drugs due to intrinsic variations in drug metabolism and drug interactions. GUIDELINES RECOMMEND TREATMENT OF OCD WITH HIGHER DOSE OF SSRIs. HOWEVER, IF AN INDIVIDUAL PATIENT IS NOT ABLE TO TOLERATE HIGHER DOSE, LOW TO MEDIUM DOSE TREATMENT CAN BE CONSIDERED. Duration of trial and dose titration A recent meta-analysis of 17 RCTs found that SSRIs separate from placebo as early as 2 weeks and that majority of improvement occurs early on in the course of treatment [20]. However, improvements seen early in the course of treatment may not be always clinically meaningful. In many patients, clinically meaningful improvements may be seen only after weeks or months of treatment. It is recommended that an adequate trial of a SSRI (or clomipramine) should be at least for 12 weeks to account for the lag in the onset of action. The APA guidelines recommend upward titration to the maximum FDA-approved doses by 4-6 weeks and continuation in that dose for another 6-8 weeks or so to determine efficacy [11]. Certain clinical and biological predictors of treatment response to SSRIs have been identified but they are not robust predictors (Table 7).Table 7: Predictors of response to SSRIsGUIDELINES RECOMMEND CONTINUING MAXIMALLY TOLERATED EFFECTIVE DOSE OF A SSRI FOR AT LEAST 12 WEEKS FOR JUDGING ITS EFFICACY. GUIDELINES ALSO RECOMMEND DOSE ESCALATION TO EFFECTIVE DOSE RANGES WITHIN 4-6 WEEKS AND CONTINUATION IN THE SAME DOSE FOR ANOTHER 6-8 WEEKS. 2. Other medications that can be tried as monotherapy in OCD Venlafaxine, a serotonin-norepinephrine reuptake inhibitor with preferential serotonergic action, has been studied in comparison to paroxetine in a double blinded study and clomipramine in a single blinded study. The studies found no difference in the efficacy between venlafaxine and the comparator agents in acute control of OCD. Given the absence of evidence from placebo-controlled trials, venlafaxine is not the first-line treatment for OCD. Hence, the guidelines consider venlafaxine as a second-line monotherapy agent in the treatment of OCD. Mirtazapine has been studied as a monotherapy in two small open-label trials with inconsistent findings. Therefore, mirtazapine cannot be recommended as monotherapy in treatment of OCD. 3. Treatment strategy for non-responders to first-line treatment Definitions of treatment outcome [21] are given in Table 8. Estimates suggest that around 40-70% patients show an adequate response to a trial of SSRI with a remission rate of 10-40% [16]. Clinicians often face the subsequent challenge of partial and non-response to SSRIs. Continuing improvement has been noticed with prolonged trial of SSRIs as discussed above. Hence, the initial trial may be continued further if there is evidence of ongoing improvement. A general treatment algorithm for OCD and for non-responders to SSRIs is shown in Figures 1 and 2 respectively.Table 8: Definitions of treatment outcome in OCDFigure 1: Treatment algorithm for treating a patient with OCD. *First line treatment chosen based on feasibility and severity of illness, #CBT/BT- Cognitive behavior therapy/Behavior therapy, @SSRI – Selective serotonin reuptake inhibitor, %rTMSrepetitive transcranial magnetic stimulation, $ - tDCS- transcranial direct current stimulation. ** Preferred for severe OCDFigure 2: Strategies for non-responders to SSRIs. SSRI-Selective serotonin reuptake inhibitors, CBT/BT-Cognitive behavior therapy/behavior therapy, rTMS- repetitive transcranial magnetic stimulationa. Switching to another medication Switching to another first-line medication has been found to be effective; experts provide a rough estimate of 40-50% response rate for the second SSRI and decreasing response rates with further trials. Switching to a second SSRI is suggested for non-responders to a first SSRI. In partial responders, changing medication may entail loss of the response to the earlier medication. Hence, switching is recommended in partial responders only if there are severe persisting symptoms or upon failure of other augmenting strategies such as CBT and atypical antipsychotics. b. Switching / Augmenting with CBT/BT It is uncertain whether initiating a combination of BT/CBT simultaneously with SSRI is advantageous compared to either treatment alone. However, CBT/BT has been proven to be effective as an augmenter in partial/non-responders to SSRIs [182223]. Where feasible, CBT/BT is a potential first-line augmenting option for partial/non-responders to SSRI treatment. c. Augmenting with another medication (Table 9)Table 9: Pharmacological augmenting agents in medications have been commonly tried as to SSRIs. and have the are the most widely studied augmenting agents of SSRIs The literature on is with including small doses and duration of treatment with both and of treatment resistance etc. recent meta-analyses of RCTs on found that as a group was significantly more effective than placebo in decreasing YBOCS a third of patients to and are consistently found to be effective as augmenting The evidence for should be with caution as it was based on a single study. A comparing and placebo of SSRI found that not separate from placebo in augmenting efficacy This study has raised questions on the efficacy of as an and have not been consistently found to be while other have not been studied Meta-analyses not any on adequate dose and duration of treatment should be used in low doses (e.g., mg of mg for a period of at least weeks for an adequate of in the should be considered after the benefits and risks of long-term BASED ON THE AND BE THE FIRST FOR PHARMACOLOGICAL agents There is a supporting the use of drugs in OCD. The agents have been studied in OCD found effective in 2 double blinded and one single blinded found effective in 2 double blinded RCTs effective in 2 small but inconsistent in two RCTs from three has to be studied BASED ON THE AND ITS BETTER TOLERABILITY, IS AS THE FIRST agents including and are reported to be effective and well in small RCTs However, due to the of the individual are recommended as second line augmenting agents along with evidence that clomipramine can be an effective augmenting Clomipramine and SSRI combination should be used with fluoxetine and as they may clomipramine related adverse effects cardiac serotonin due to pharmacokinetic interactions. Clomipramine of SSRI may be tried but adequate to be in the potential adverse effects of the Mirtazapine has been found to the response with no significant benefits and may be considered as an augmenting agent in partial responders and Other augmenting agents and have not been found effective and are not recommended as augmenting The and efficacy of and drugs have to be studied they are recommended for routine clinical has been found to have acute effects in a which needs and the strategy can be recommended for routine clinical Other strategies there to be some short-term benefits for clomipramine in treatment patients, the benefits are This is not available in and is not recommended at present for clinical There are a few trials the of higher than recommended doses of SSRIs to mg of mg of in This strategy should be considered and may be used only in patients after other OF of patients not to available pharmacological and and treatments the have been tried in has not been for the treatment of OCD. in the of and not provide evidence for the efficacy of Hence, is not recommended as a treatment for OCD and may be considered for the treatment of comorbid conditions severe and disorders, if 2. transcranial magnetic the of and of or decreasing their based on the of stimulation. The in OCD are usually not with available of has been tried in which have with other in OCD. trials of low or high over either have but low over supplementary and However, the evidence has not been very the have to be in with There is no evidence that effects for longer than the trial The guideline as an for further and not for routine clinical 3. direct current is another and which either or the of the depending on the of the There are only a few and an open-label trial on in OCD. It has to be more it can be recommended for clinical use in OCD. in specific of the which is to be in OCD. can be with the of or with the of and a of as are in treatment OCD in a few to the these are generally employed in treatment patients (Table in the of studies that around of patients improve over months There is some that may be more effective in OCD and that its efficacy may be similar to that of brain may be associated with short-term and adverse effects including personality and adverse effects although rates are not criteria for brain brain is a high of in the the of action is it is to for OCD has been in controlled studies of and A recent meta-analysis found a rate of with a YBOCS of around is an and is associated with and adverse Further, the needs to be which may be can be recommended in OCD patients (Table after regarding the and of the The are not in and the are only one aspect of a comprehensive treatment which should may be considered only in patients after of patients for treatment severity of illness and Patients should be explained about the of benefits and They should be by an of a a and a for for The treatment should be conducted of a of and with of adverse criteria for to are shown in Table FOR OCD (TABLE Cognitive / and in has been shown to be in the treatment of OCD All treatment guidelines have suggested the use of CBT as a first-line treatment CBT for OCD is a first-line treatment option for OCD. is the most important of CBT along with When are monotherapy may be recommended in mild to moderately ill In severely ill patients a combination of CBT and SSRI is CBT as an strategy It is uncertain whether initiating a combination of and SSRI is advantageous compared to either treatment alone. However, CBT/BT is found to be effective in augmenting SSRIs in partial/non-responders to SSRIs [34]. A recent study found CBT to be to and placebo in augmenting SSRIs in OCD Patients in the CBT group

The authors investigated trazodone as a hypnotic for depressed patients who had persistent, exacerbated, or new insomnia while taking either fluoxetine or bupropion. Seventeen depressed patients who had insomnia while taking fluoxetine or bupropion were given either trazodone or placebo in a double-blind crossover trial. Sleep was assessed by self-report with the Pittsburgh Sleep Quality Index and the sleep items of the Yale-New Haven Hospital Depressive Symptom Inventory. Improvement with trazodone, but not with placebo, was shown by the total Pittsburgh index scores and Yale-New Haven inventory total sleep scores and by the Pittsburgh index measures of sleep duration and Yale-New Haven inventory measures of early morning awakening, and there was a trend toward improvement in the Yale-New Haven inventory item regarding middle of the night awakenings. Subjective sleep quality and sleep latency also showed a trend toward improvement, but the Pittsburgh index measures of sleep efficiency and disturbances and the Yale-New Haven inventory item regarding difficulty falling asleep were unaffected by trazodone. One patient dropped out because of excessive daytime sedation with trazodone, and another dropped out because of nonresponse to placebo. Of the completers, 67% experienced overall improvement in sleep with trazodone according to a priori criteria, whereas only 13% experienced improvement with placebo. Trazodone is an effective hypnotic for patients with antidepressant-associated insomnia.

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Management of Depression in Parkinson’s Disease

How the trajectory of response to medication (and placebo response) varies among selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), benzodiazepines and across anxiety disorders is unknown. We performed a meta-analysis using weekly symptom severity data from randomized, parallel-group, placebo-controlled trials of SSRIs, SNRIs, and benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in anxiety using Bayesian hierarchical models. Across 122 trials (N=15,760), SSRIs, SNRIs, and benzodiazepines produced significant improvement in anxiety compared to placebo. Benzodiazepines produced faster improvement by the first week of treatment (p<0.001). By week 8, the response for benzodiazepines and SSRIs (p=0.103) and SNRIs (p=0.911) did not differ nor did SSRIs and SNRIs differ (p=0.057), although for patients with generalized anxiety disorder (GAD), the benzodiazepines produced greater improvement than SNRIs at week 8 (difference-12.42, CrI: -25.05 to -0.78, p=0.037). Medication response was similar across anxiety disorders except for benzodiazepines, which produced greater improvement over the first 4weeks compared to SSRIs and SNRIs in panic disorder. For SSRIs and SNRIs, women improved more than men, and for benzodiazepines, older patients improved more compared to younger patients. Finally, placebo response plateaued by week 4 of treatment, and, at week 8, social anxiety disorder trials had lower placebo response compared to other anxiety disorders. Benzodiazepines show early improvement compared to SSRIs and SNRIs. However, by week 8, all treatments yield similar results. Patient characteristics influence the improvement trajectory and magnitude, suggesting potential for personalized medication selection.

This new version of the psychotic depression algorithm has been developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The most effective treatment modality for inpatients with severe psychotic depression is electroconvulsive therapy. The first-line psychopharmacological treatment is a combination of an antidepressant (either a tricyclic or a selective serotonin reuptake inhibitor) and an antipsychotic. If one of these combinations has failed, consider switching to the other. If both combinations have failed, the next psychopharmacological option would be to augment the combination with lithium. Another option, though with limited evidence, is monotherapy with clozapine. If there is a good reason to avoid combination therapy with an antipsychotic, then a trial of monotherapy with a TCA or an SSRI can be supported. If that fails, adding an antipsychotic or ECT should be considered.

To determine the associations between PTSD, psychotropic medication use, and the risk for dementia. Retrospective cohort. Nationwide sample of US veterans (N = 417,172) aged ≥56 years during fiscal year (FY) 2003 without a diagnosis of dementia or mild cognitive impairment at baseline (FY02-03) and ≥1 clinical encounter every 2 years during follow-up (FY04-12). Demographic characteristics; diagnosis of PTSD, dementia, and medical and psychiatric comorbidity (defined by ICD-9 codes); and psychotropic medication use including selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), novel antidepressants (NA), benzodiazepines (BZA), and atypical antipsychotics (AA). Cox proportional hazard models examined for associations between PTSD diagnosis, psychotropic medication use, and risk for a dementia diagnosis. PTSD diagnosis significantly increased the risk for dementia diagnosis (HR = 1.35; [95% CI = 1.27-1.43]). However, there were significant interactions between PTSD diagnosis and use of SSRIs (P < .001), NAs (P = .014), and AAs (P < .001) on the risk for dementia diagnosis. HR for dementia diagnosis among veterans diagnosed with PTSD and not using psychotropic medications was 1.55 [1.45-1.67]. Among veterans diagnosed with PTSD prescribed SSRI, SNRI, or AA, HR for dementia diagnosis varied by drug class use ranging from 1.99 for SSRI to 4.21 for AA, relative to veterans without a PTSD diagnosis and no psychotropic medication receipt. BZAs or SNRIs use at baseline was associated with a significantly increased risk for dementia diagnosis independent of a PTSD diagnosis. PTSD diagnosis is associated with an increased risk for dementia diagnosis that varied with receipt of psychotropic medications. Further research would help to delineate if these findings are due to differences in PTSD severity, psychiatric comorbidity, or independent effects of psychotropic medications on cognitive decline.

BackgroundThis is a new algorithm from the Psychopharmacology Algorithm Project at the Harvard South Shore Program, focused on generalized anxiety disorder (GAD) in older adults. Pertinent articles were identified and reviewed.ResultsSelective serotonin reuptake inhibitors (SSRIs) are considered to be first-line medications, with a preference for sertraline or escitalopram. If avoiding sexual side effects is a priority, buspirone is an option for the relatively healthy older adult. If response is inadequate, the second recommended trial is with a different SSRI or one of the serotonin-norepinephrine update inhibitors (SNRIs), venlafaxine or duloxetine. For a third medication trial, additional alternatives added to the previous options now include pregabalin/gabapentin, lavender oil, and agomelatine. If there is an unsatisfactory response to the third option chosen, quetiapine may be considered. We recommend caution with the following for acute treatment in this population: benzodiazepines and hydroxyzine. Other agents given low priority but having some supportive evidence were vilazodone, vortioxetine, mirtazapine, and cannabidiol. Acknowledging that the median age of onset of GAD is in early adulthood, many patients with GAD will have been started on benzodiazepines (or other medications that require caution in the elderly) for GAD at a younger age. These medications may be continued with regular observation to see if the potential harms are starting to exceed the benefits and a switch to other recommended agents may be justified.

The selective serotonin reuptake inhibitors (SSRIs) are extensively used for the treatment of multiple psychiatric conditions. In vitro and ex vivo data with these agents indicate they may have varying degrees of antiplatelet activity via multiple receptors. Reports of bleeding in patients receiving SSRIs appeared soon after their introduction. A review of the literature suggests SSRI therapy may increase the risk of bleeding especially with concomitant aspirin or nonsteroidal anti-inflammatory agents. Clinicians should exercise caution when prescribing these agents in high risk patients and maintain awareness of the potential contribution of SSRIs to unexplained bleeding episodes.