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Ähnlich wie Antipsychotic induced diabetes 6.23
Ähnlich wie Antipsychotic induced diabetes 6.23 (20)
Antipsychotic induced diabetes 6.23
- 1. Non-ketonic Hyperglycemia Hyperosmolar State Secondary to Clozapine Therapy Michael Nguyen, Pharm. D. Candidate 2017 MCPHS University
- 2. Objectives After this presentation, the audience should be able to 1. Appreciate the risks of metabolic effects (specifically hyperglycemia) from antipsychotic medications 2. Explain how to manage acute non-ketonic hyperglycemia hyperosmolar state (HHS). 3. Make recommendations for patients with new onset diabetes secondary to antipsychotic therapy For the purposes of this discussion Atypical antipsychotics = AAPs = 2nd generation antipsychotics = SGA’s Typical antipsychotics = TAPs = 1st generation antipsychotics = FGA’s
- 3. Meet the patient AM is a 67 year old male who presents to Lahey ER with a CC of altered mental status and lethargy with increased thirst and urination. Nurses at his locked psychiatric facility noticed he was behaving differently. He became dizzy and fell, causing him to be brought in to Lahey. There was no documentation of head trauma. Of note, he was recently treated for furunculosis with Keflex
- 4. PTA medications Schizoaffective disorder HLD± HTN± INS± BPH± ANX± Smoking Cessation Misc. Clozapine 150 mg PO daily Lithium 300 mg PO daily Haloperidol 0.5 mg PO PRN agitation Atorvastatin 20 mg PO daily Metoprolol tartrate 175 mg by mouth BID Melatonin 3 mg HS Diphen** 25 mg tablet PO HS PRN for insomnia Tamsulosin 0.4 mg PO daily Lorazepam 1 mg PO Q6H PRN for anxiety Nicotine Polacrilex 4 mg lozenge PRN for smoking cessation Maalox Advanced, 30 mL PO Q6H PRN Clotrimazole 1% cream every morning and evening Vit. D3 1ooo IU QD B12 1000 mcg QD Docusate 100 mg capsule every morning and evening Milk of Magnesium 400 mg / 5 mL suspension, 30 mL PO QD PRN Sennosides 8.6 mg PO daily ± HLD – Hyperlipidemia, HTN – Hypertension, INS – Insomnia, BPH – Benign prostate hyperplasia, ANX – Anxiety ** diphenhydramine Medications Held on admission New In-Patient Meds (3 day stay) Maalox Advanced, 30 mL PO Q6H PRN Diphenhydramine 25 mg tablet, PO HS PRN for insomnia Lithium 300 mg PO daily Lorazepam 1 mg PO Q6H PRN for anxiety Sennosides 8.6 mg PO daily (6/5) Ceftriaxone (6/6) Cefazolin 1 g Q8h (6/6) Lithium CR 300 BID Normal Saline IV bolus & Continuous Heparin 5000 u SC BID Insulin aspart and glargine Saccharomyces Boulardii BID
- 5. Schizoaffective disorder vs. Schizophrenia • Diagnostic and Statistical Manual of Mental Disorders (DSM-5) definitions • Schizophrenia – a serious mental illness characterized by at least 2 of the following symptoms for a minimum of 6 months and include at least one month of active symptoms. (which interfere with social/occupational function) ▫ Delusions ▫ Hallucinations ▫ Disorganized speech and behavior ▫ Grossly disorganized or catatonic behavior ▫ Negative symptoms (diminished emotional expression) DSM-5 2013;150(1):3-10 DSM-5 2013;150(1):21-25
- 6. Hyperosmolar Hyperglycemia State Diagnostic Criteria Diagnostic value Our Patient Blood Glucose > 600 mg / dL 813 mg / dL Arterial pH > 7.3 7.38 Bicarbonate > 15 mEq / L 24 mEq / L Mild Ketonuria / Ketonemia Positive Urine ketones negative Effective Serum Osmolality > 320 mOsm / kg H2O 303 mOsm / kg Diabetes Care 2009;32(7):1335-1343 Effective serum osmolality = 2(Na) + (Glucose)/18
- 7. My Questions How did the endocrinologist associate HHS with clozapine? What is the nature of clozapine induced diabetes mellitus (DM)? Did we properly treat AM’s HHS? How do you manage a patient with diabetes induced by clozapine?
- 8. Atypical antipsychotics and glucose dysregulation: a systematic review 4 Case series 13 Epidemiological studies 8 Clinical studies The case series studies occurred in the early 2000s and showed a potential relationship between patients using atypicals (Clozapine, Olanzapine, Risperidone and Quetiapine) and new onset DM Only 8 reports compared the risk of developing DM directly or indirectly between SGAs and FGAs Only 2 were prospective 7 of the 8 suggested that SGAs had significantly increased risk of new onset DM vs FGAs 5 found use of Olanzapine was associated with significantly greater risk of blood glucose or insulin levels vs. risperidone or control 8 studies evaluated new-onset DM among individual SGAs vs. other SGAs or FGAs or non-users 5 Studies evaluated clozapine suggested that glucose levels or other markers of glucose/insulin homeostasis were significantly increased in clozapine group vs. FGA or controls 2 studies found no difference in risk of developing DM with clozapine while 2 other found greater risk Schizophrenia Research. 2004;71(2-3):195-212
- 9. Clozapine-associated Diabetes Hyperglycemic events associated with Clozapine use were searched using FDA Medwatch (Jan 1990 – Feb 2001) Medline (Jan 1985 – Feb 2001) Koller E. et al. 2001 n = 384 cases
- 10. Clozapine-associated Diabetes cont. Koller E. et al. 2001
- 11. Association of Diabetes Mellitus with Use of Atypical Neuroleptics in the Treatment of Schizophrenia • Retrospective study of ALL patients in VA database with a diagnosis of schizophrenia during fiscal year of 1999 (October 1, 1998 to September 30, 1999) • Hypothesis – Prescription of atypical neuroleptics (SGA’s) is associated with an increased prevalence of diabetes. AJP. 2002;159(4):561-566Sernyak, Leslie, Alarcon, et al.
- 12. Full of confounding? Patients with Dx of Schizophrenia (Oct 1998 – Sep 1999) n = 38,632 15,984 (41.4%) Received typical antipsychotics 22648 (58.6%) received atypical antipsychotics Baseline Characteristics The groups were significantly different in all characteristics except for Hispanic or Degree of VA compensation Significantly • Younger • Have less income • More female • Incidence of another psychiatry diagnosis • They also lived further from VA hospital • Likely hood of being hospitalized AJP. 2002;159(4):561-566 Association of Diabetes Mellitus with Use of Atypical Neuroleptics in the Treatment of Schizophrenia
- 13. What were the odds of DM with atypicals? • Younger age groups (<60) had higher odds of DM diagnosis • For the entire group (all ages) All atypicals had significantly greater odds of DM diagnosis except for risperidone • Although there was no difference in older groups, look at the rate of diabetes in either group AJP. 2002;159(4):561-566
- 14. Key Points of the articles Koller et. al. Sernyak et. al. • Most hyperglycemic events associated with clozapine occur within 6 months of therapy initiation. • There are some cases where discontinuing clozapine therapy may reverse hyperglycemia / glucose dysregulation • 15% of the new-onset diabetes patients developed blood sugars of > 700 mg/dL • This study did not show any correlation with dose and severity of the hyperglycemic event. • Patients receiving SGAs are 9% more likely to have DM than those on conventional antipsychotics (p = 0.002) • Younger aged patients with schizophrenia who take atypicals have significantly greater odds of having DM diagnosis vs. those not taking atypicals. The odds are not significant in older patients (60+) • This supports that older patients are more likely to get diabetes and metabolic dysregulation due to the nature of the disease.
- 15. Back to our patient… Diagnostic Criteria Diagnostic value Our Patient Blood Glucose > 600 mg / dL 813 mg / dL Arterial pH > 7.3 7.38 Bicarbonate > 15 mEq / L 24 mEq / L Mild Ketonuria / Ketonemia Positive Urine ketones negative Effective Serum Osmolality > 320 mOsm / kg H2O 303 mOsm / kg Diabetes Care 2009;32(7):1335-1343 Effective serum osmolality = 2(Na) + (Glucose)/18
- 16. Treatment regimen for hyperosmolar hyperglycemia state Diabetes Care 2009;32(7):1335-1343
- 17. So… what ever happened to our patient? 0 5 10 15 20 25 30 35 40 0 100 200 300 400 500 600 700 800 6/4/16 12:00 6/5/16 0:00 6/5/16 12:00 6/6/16 0:00 6/6/16 12:00 6/7/16 0:00 6/7/16 12:00 6/8/16 0:00 AM’s 3 day Clinical Course Glucose (g/dL) Potassium (mmol/L) Rapid/Short Insulin (units) Glargine (units)
- 18. Review of outpatient monitoring with antipsychotics Baseline 4 weeks 8 weeks 12 weeks Quarterly Annually Every 5 years Personal/Family Hx X X Weight (BMI) X X X X X Waist Circumf. X X Blood Pressure X X X Fasting blood gluc. X X X X Fasting Lipid panel X X Diabetes Care. 2004;27(2):596-601 “Consider switching to a less offensive agent if the patient develops a weight gain of 5% or more during any time of treatment with SGA or those who develop worsening glycemia or dyslipidemia”
- 19. Patient discharge • AM was discharged on 6/7/16 (2 days inpatient) to Bedford VA to be followed up with psychiatry and endocrinology Schizoaffective disorder HLD± HTN± INS± BPH± ANX± Smoking Cessation Misc. Clozapine 150 mg PO daily Lithium 300 mg PO daily Haloperidol 0.5 mg PO PRN agitation Atorvastatin 20 mg PO daily Metoprolol tartrate 175 mg by mouth BID Melatonin 3 mg HS Diphen** 25 mg tablet PO HS PRN for insomnia Tamsulosin 0.4 mg PO daily Lorazepam 1 mg PO Q6H PRN for anxiety Nicotine Polacrilex 4 mg lozenge PRN for smoking cessation Maalox Advanced, 30 mL PO Q6H PRN Clotrimazole 1% cream every morning and evening Vit. D3 1ooo IU QD B12 1000 mcg QD Docusate 100 mg capsule every morning and evening Milk of Magnesium 400 mg / 5 mL suspension, 30 mL PO QD PRN Sennosides 8.6 mg PO daily New Medication at D/C Insulin aspart sliding scale and insulin glargine 40 units SC HS Continue with PTA medications
- 20. Any Questions ? References • Malaspina D, Owen MJ, Heckers S, et al. Schizoaffective Disorder in the DSM-5. Schizophrenia Research. 2013;150(1):21-25. doi:10.1016/j.schres.2013.04.026. Accessed 6/18/2016 • Tandon R, Gaebel W, Barch DM, et al. Definition and description of schizophrenia in the DSM-5. Schizophrenia Research. 2013;150(1):3-10. doi:10.1016/j.schres.2013.05.028. • Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic Crises in Adult Patients With Diabetes. Diabetes Care. 2009;32(7):1335- 1343. doi:10.2337/dc09-9032. • Koller E, Schneider B, Bennett K, Dubitsky G. Clozapine-associated diabetes. The American Journal of Medicine. 2001;111(9):716-723. doi:10.1016/s0002-9343(01)01000-2. • Taylor M, Perera U. NICE CG178 Psychosis and Schizophrenia in Adults: Treatment and Management - an evidence-based guideline. The British Journal of Psychiatry. 2015;206(5):357-359. doi:10.1192/bjp.bp.114.155945. • Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care. 2004;27(2):596-601. doi:10.2337/diacare.27.2.596. • Jin H, Meyer JM, Jeste DV. Atypical antipsychotics and glucose dysregulation: a systematic review. Schizophrenia Research. 2004;71(2-3):195- 212. doi:10.1016/j.schres.2004.03.024 • Clozapine and the Risk of Neutropenia: A Guide for Healthcare Providers. Clozapine REMS. https://www.clozapinerems.com/cpmgclozapineui/rems/pdf/resources/clozapine_rems_a_guide_for_healthcare_providers.pdf. Published September 2015. Accessed June 23, 2016. • Sernyak MJ, Leslie DL, Alarcon RD, Losonczy MF, Rosenheck R. Association of Diabetes Mellitus With Use of Atypical Neuroleptics in the Treatment of Schizophrenia. American Journal of Psychiatry AJP. 2002;159(4):561-566. doi:10.1176/appi.ajp.159.4.561.
Hinweis der Redaktion
- Tell audience the lab values Cephalexin Ceftriaxone x1 dose Cefazolin (no documented reason for continuation of Abx) (click) Nicotine was never given in patient. Patient was treated with relatively low doses for psychosis. Lithium usually 300 mg TID Clozapine usually titrated to 300-900 mg QD However, patient seemed to be stable on these doses. Metoprolol is a high dose but falls below its maximum of 450 mg daily for HTN.
- DSM 5 criteria for Schizoaffective disorder Unterurrupted period of MDD (2 week period of 5 or more Category A symptoms) concurrent with schizophrenia 1. Depressed mood most of the day, almost every day, indicated by your own subjective report or by the report of others. This mood might be characterized by sadness, emptiness, or hopelessness. 2. Markedly diminished interest or pleasure in all or almost all activities most of the day nearly every day. 3. Significant weight loss when not dieting or weight gain. 4. Inability to sleep or oversleeping nearly every day. 5. Psychomotor agitation or retardation nearly every day. 6. Fatigue or loss of energy nearly every day. 7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day. 8. Diminished ability to think or concentrate, or indecisiveness, nearly every day. 9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide. Depressed mood. Delusions or hallucinations for 2 or more weeks in the absence of major mood episode (Depressive or Manic) during the lifetime duration of the illness Symptoms meet criteria for a Major Mood Episodes are present for the majority of the total duration of active and residual portions of the illness The disturbance is not attributable to the effects of a substance or anther medical condition. Today, therapy for schizophrenia and schizoaffective disorder revolve around Atypicals Decreased Extrapyramidal effects! Effects on both POSITIVE and NEGATIVE symptoms Positive symptoms include: Delusions, voices, paranoia, ideas of reference (talking TV), visual hallucinations (disturbances of thoughts and perceptions Clozapine Notes First atypical approved in United States in 1989! NO EPS symptoms Today, last line LOTS of weight gain MOA – Pulsatile D2 blockade Low EPS and low hyperprolactinemia issues GOAL Dosage range 300-900 mg / day, titrated 25-50 mg everyday over a 2 week period Common ADRs SALIVATION, Seizure risk, hypotension, bradycardia, WEIGHT GAIN Metabolized by 1A2 (cigarettes) and 3A4 (carbamazepine) – Watch for inducers. REMS Qwk x 6 mo, then QoW x 6 mo, then Q4w thereafter NICE guidelines say that Clozapine should be utilized as an agent after 2 other atypical antipsychotics have failed Patient has schizoaffective disorder. Which of his drugs covers the “mood” portion of his illness? Management of schizoaffective disorder Lithium at a goal level of 0.4-1 for management Lithium is the only drug that covers both Mania and Depression The patient was on a really low dose at home 300 mg PO daily? ADRs: Leukocytosis (the patient!), Hypothyroid (Patient!), Weight gain, Diabetes Insipidus (Na wasting… Patient), Tremor (treat w/ BB), NEPHROTOXIC (patient) Common drug interactions: Lower (theophylline and excess sodium), Higher (ACE/ARB, Diuretics, NSAIDs, Carbamazepine (SIADH reduces Na), Na depletion. Caffeine is variable.
- However, when calculated with BUN consideration 2(Na) + (BUN)/2.8 + (Glucose)/18 = 319.24 Precipitating factors – Infection, CVA, Alcohol abuse, pancreatitis, MI, Trauma, DRUGS ENDOCRINOLOGIST associated the patient’s HHS with clozapine.
- This was a systematic review, not a meta analysis There are very limited prospective studies. I could not find much with my own search. It was more of a display of multiple studies and provided no further statistical conclusions. Methods were not described Professional disclosures were not provided Results were difficult to ascertain as they were presented in paragraph form. The presented data made it easier for providers at the time to see a relationship between SGAs and DM
- Study design – Retrospective epidemiologic study. Medline search for published cases (Jan 1985-Feb 2001) and MedWatch Drug Surveillance System (from Jan 1990 to Feb 2001). Drug utilization data obtained through IMS. Solely a descriptive study. Purpose – TO show an association with clozapine use and hyperglycemic events, more importantly new-onset diabetes and preexisting diabetes exacerbations Population – Cases were combined to prevent double counting. Intervention – NONE Endpoints – For each case, the investigators assessed “documentation “ of diabetes, severity of illness, new onset hyperglycemia, demographics, time to onset of hyperglycemia and effect of drug discontinuation. Definition of new-onset diabetes = FBG > 126 mg/dL, random BG > 200 mg/dL, elevated A1C (>6.5), presence of metabolic acidosis or ketosis, OR physician institution of antidiabetic medication. Statistics – all statistics were descriptive. No analytical statistics. Results N = 384 cases of clozapine-associated DM or hyperglycemia (238 from US and 146 international) (included 39 cases in 24 publications) 323 New-onset hyperglycemia 171 patients fit the criteria for diabetes Of those diagnosed by FBG values, all but 4 had FBG > 140 152 patients did not have enough lab data Of these patients, 49 were using antidiabetic medications. of these, 7 patients had acidosis or ketosis 54 reports of worsening preexisting diabetes after clozapine 7 cases – unclear if preexisting or new-onset Demographics (Table 1 on article) age was known in 89% of cases, majority of participants Sex ratio (Male:Female) – 92% known in all cases, overall more males However, when split up amongst type of hyperglycemia, more females in each section (except for overall new-onset hyperglycemia) Time to onset 76% of cases provided temporal information. In most cases (175) , hyperglycemic events occurred within 6 months of starting clozapine. 141 of the 171 (82% known) new-onset diabetes patients had temporal information 38 (27%) of these patients diabetes was diagnosed within the first month of clozapine therapy 79 (56%) within the first 3 months One patient developed diabetes after a 500 mg dose! 47 of the 54 patients (87%) preexisting patients had temporal information 18 (38%) had exacerbation in first month 30 (64%) had exacerbation within 3 months. Dose of clozapine was available in 83% of cases (320) overall had a mean dose of 362 + 208 mg . Lowest dose that caused hyperglycemic event OR new-onset hyperglycemia – 25 mg!!! No correlation between dose and severity of event. Correlation coefficients were all positive but all below 50% Drug levels were not available Concomitant drugs No one was on steroids, 1 person on Megace Most common concurrent meds were – Valproic acid, Lithium, Benzatropine, Major tranquilizers, thyroid hormone, H2 blockers and PPIs Reversibility 110 discontinuations Only 54 of the 110 had follow up data 42 reported to improve 26 no longer required diabetes treatment 18 had blood sugar levels return to normal. 11 had no change 12 patients were rechallenged – 9/12 deteriorated. glycemic control occurred again in 4 patients after d/c of rechallenge. 51 cases of 323 new onset hyperglycemia patients had BG > 700 mg/dL (table 2) at least 63% of these cases occurred within first 3 months. 26 of these patients had ketosis / acidosis. 80 cases of Ketosis / acidosis, 73 of these cases were with new-onset diabetes. Researchers conclude there is a correlation but no causality due to the nature of the study
- Given the limited data on AM, we could assume that he was recently started on Clozapine since he is not at the most common target dose of 300-900 mg daily Most cases occur within 6 months of use. However, the investigators not that the range for time to onset was 2 days – 5 years Most hyperglycemic events associated with clozapine occur within 6 months of therapy initiation. There are some cases where discontinuing clozapine therapy may reverse hyperglycemia / glucose dysregulation 15% of the new-onset diabetes patients developed blood sugars of > 700 mg/dL This study did not show any correlation with dose and severity of the hyperglycemic event. Limitations of this study Medwatch is voluntary, misses lots of data, there is no control group. A larger number of case reports would be more useful to see a better relationship
- The atypicals available at the time included Clozapine, Olanzapine, Quetiapine and Risperidone Study – Retrospective 4 month observation of national VA databases. (data was Jun – Sep 1999) Population - All patients with Dx of Schizophrenia (ICD 9 cod 295) were included. N = 38,632 15,984 (41.4%) Received typical antipsychotics 22648 (58.6%) received atypical antipsychotics (separated by last neuroleptic prescribed and 7 days prior) 8.9% of these patients also had a FGA 94% of these patients remained on the same one through the 4 month period. Exclusion from analysis - If no neuroleptic prescription was written for the entire 4 month period Interventions FGA’s only– 15,985 SGA’s + FGA – 22,648 Clozapine – 1207 Olanzapine – 10970 Quetiapine – 955 Risperidone - 9903 Endpoint Diagnosis of diabetes = at least 1 outpatient encounter or inpatient stay with ICD codes 250 (diabetes) during 4 month period. .
- Statistics Baseline characteristics were compared with T-test (for continuous data) and X squared test (nominal data) Endpoint was analyzed with Logistic regression to calculate ODDS ratio. This addresses potentially confounding data. Data was stratified for age groups < 40 , 40 – 49, 50 -59, 60 – 69, and over 70 years 4 Dichotomous variables (each atypical neuroleptic) had repeated analysis to determine ODDS ratio for each drug in each age strata. A composite of all age groups were combined to form a single analysis with age as the covariate to determine population-wide prevalence of diabetes Results (see next page) (previous page) Study – Retrospective 4 month observation of national VA databases. (data was Jun – Sep 1999) Population - All patients with Dx of Schizophrenia (ICD 9 cod 295) were included. N = 38,632 15,984 (41.4%) Received typical antipsychotics 22648 (58.6%) received atypical antipsychotics (separated by last neuroleptic prescribed and 7 days prior) 8.9% of these patients also had a FGA 94% of these patients remained on the same one through the 4 month period. Exclusion from analysis - If no neuroleptic prescription was written for the entire 4 month period Interventions FGA’s only– 15,985 SGA’s + FGA – 22,648 Clozapine – 1207 Olanzapine – 10970 Quetiapine – 955 Risperidone - 9903 Endpoint Diagnosis of diabetes = at least 1 outpatient encounter or inpatient stay with ICD codes 250 (diabetes) during 4 month period.
- All atypicals = Clozapine, Olanzapine, Quetiapine and Risperidone Major limitation – small data window – patient could have taken atypical before the 4 month window and switched to typical only therapy? No weight data was available. No compliance data was analyzed. Dependence on ICD 9 codes isn’t 100% accurate (look at our Lahey problem lists) Study – Retrospective 4 month observation of national VA databases. Population - All patients with Dx of Schizophrenia (ICD 9 cod 295) were included. N = 38,632 15,984 (41.4%) Received typical antipsychotics (separated by last neuroleptic prescribed and 7 days prior) 22648 (58.6%) received atypical antipsychotics 8.9% of these patients also had a FGA 94% of these patients remained on the same one through the 4 month period. Exclusion from analysis - If no neuroleptic prescription was written for the entire 4 month period Interventions FGA’s only– 15,985 SGA’s + FGA – 22,648 Clozapine – 1207 Olanzapine – 10970 Quetiapine – 955 Risperidone - 9903 Endpoint Diagnosis of diabetes = at least 1 outpatient encounter or inpatient stay with ICD codes 250 (diabetes) during 4 month period. Statistics Baseline characteristics were compared with T-test (for continuous data) and X squared test (nominal data) Endpoint was analyzed with Logistic regression to calculate ODDS ratio. This addresses potentially confounding data. Data was stratified for age groups < 40 , 40 – 49, 50 -59, 60 – 69, and over 70 years 4 Dichotomous variables (each atypical neuroleptic) had repeated analysis to determine ODDS ratio for each drug in each age strata. A composite of all age groups were combined to form a single analysis with age as the covariate to determine population-wide prevalence of diabetes
- However, when calculated with BUN consideration 2(Na) + (BUN)/2.8 + (Glucose)/18 = 319.24 Precipitating factors – Infection, CVA, Alcohol abuse, pancreatitis, MI, Trauma, DRUGS
- NS was given 6/5 0224 0402 (1000 mL/hr = 2L total) and 6/6 0833 0933 (1000 mL/hr) Continuous NS 100 mL/hr was started at 6/5 0323 D/C at 6/7 1722 As you can see, this patient clearly has HHS not DKA because he is very responsive to insulin therapy. He responded very well to the 8 units IV bolus of Regular insulin . Blood sugar dropped from 815 to 536 (35% drop)
- So what do you guys think should happen? Should clozapine be discontinued?
- I disagreed with that Lithium 300 mg PO daily as this resulted in the low lithium level PTA. However, he is going to follow up with his psychiatrist to revaluate his therapy. I do agree with the increase in basal insulin as his glucose levels are still quite high.