Newer generation antidepressant drugs (ADs) are widely used as the first line of treatment for major depressive disorders and are considered to be safer than tricyclic agents. In this critical review, we evaluated the literature on adverse events, tolerability and safety of selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, bupropion, mirtazapine, trazodone, agomelatine, vilazodone, levomilnacipran and vortioxetine. Several side effects are transient and may disappear after a few weeks following treatment initiation, but potentially serious adverse events may persist or ensue later. They encompass gastrointestinal symptoms (nausea, diarrhea, gastric bleeding, dyspepsia), hepatotoxicity, weight gain and metabolic abnormalities, cardiovascular disturbances (heart rate, QT interval prolongation, hypertension, orthostatic hypotension), genitourinary symptoms (urinary retention, incontinence), sexual dysfunction, hyponatremia, osteoporosis and risk of fractures, bleeding, central nervous system disturbances (lowering of seizure threshold, extrapyramidal side effects, cognitive disturbances), sweating, sleep disturbances, affective disturbances (apathy, switches, paradoxical effects), ophthalmic manifestations (glaucoma, cataract) and hyperprolactinemia. At times, such adverse events may persist after drug discontinuation, yielding iatrogenic comorbidity. Other areas of concern involve suicidality, safety in overdose, discontinuation syndromes, risks during pregnancy and breast feeding, as well as risk of malignancies. Thus, the rational selection of ADs should consider the potential benefits and risks, likelihood of responsiveness to the treatment option and vulnerability to adverse events. The findings of this review should alert the physician to carefully review the appropriateness of AD prescription on an individual basis and to consider alternative treatments if available.
I Do not remember ever to have refus'd any thing you have desir'd of me, which I take to be a greater Compliment to you, than to my self; since for a Young man to make none but Reasonable Desires, is yet more extraordinary, than for an Old man to think them so. That which you made me some time since, and have so often renew'd, I have at last resolv'd to comply with, as well as the rest; and if I live, will leave you some Memoirs of what has pass'd in my Publick Imployments, especially those abroad, which reach'd from the Year 1665, to 1678. and run through the most Important Foreign Negotiations of the Crown, with great connexion of Affairs at Home, during this Period, and the [Page] Revolutions it produc'd. The Confidence of the King, my Master, and of His Chief Ministers, as well as that of others abroad, gave me the advantage to discern and observe the true Springs and Motions of Both, which were often mistaken in Court, and in Parliament, and thereby fasten'd many Suspicions, Confidences, Applauses, Reproaches, upon Persons, and at times where they were very undeserved. Twenty years of my Life I pass'd in Publick Thoughts and Business, from the Thirty second, to the Fifty second year of my Age, which I take to be the part of a Man's Life fittest to be dedicated to the Service of His Prince, or State; the rest being usually too much taken up with his Pleasures, or his Ease. The native love of my Country, and its ancient Legal Constitutions, would not suffer me to enter into any Publick Affairs, till the way was open'd for [Page] the King's Happy Restauration in 1660. and in 1680. you know I sent you to acquaint the King with my Resolutions to pass the remainders of my Life like as good a private Subject, as any he had; but never more to meddle with any Publick Imployment. All the rest of my Age before, and since that period, I have taken no more notice of what pass'd upon the Publick Scene, than an Old man uses to do of what is acted on a Theatre, where he gets as easie a Seat as he can, entertains himself with what passes upon the Stage, not caring who the Actors are, or what the Plot, nor whether he goes out before the Play be done. Therefore you must expect nothing from me out of the compass of that time, nor any thing of that it self, with much application or care, further than of Truth. You know how lazy I am in my Temper, how uneasie in my Health, how weak my Eyes, and [Page] how much of my time passes in Walking or Riding, and thereby fencing all I can against two cruel Diseases that have for some time pursu'd me So that I doubt the satisfaction you expect, will be chiefly owing to ill Health, or ill Weather, which yet are not like to fail at my Age, and in our Climate. For the rest, if you find any thing either Instructing or Diverting in what I shall write upon this Subject, you may attribute it wholly to the Kindness and Esteem I have for you, without which I should not have given my self the trouble of such Recollections: And as I intend them for Your Use, so I desire no Other may be made of them during my Life; when that is ended, neither They nor You will be any more in my care; and whatever I leave of this or any other kind, will be in your disposal. I am the gladder, and it is but just, that my Publick Imployments [Page] should contribute something to your Entertaiment, since they have done so little to your Fortune; upon which I can make you no excuses: 'Twas a thing so often in my Power, that it was never in my Thoughts, which were turn'd always upon how much Less I needed, rather than how much More. If yours have the same turn, you will be but too Rich; if the contrary, you will be ever Poor.
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Upon the first Meeting of the Parliament, the Duke of Buckingham, to ingratiate himself with the House of Commons (whose ill humour began to appear against those they esteem'd the chief Authors of the War) had desir'd leave of that House, that he might be heard there in his own defence upon that subject. In his Speech, among many endeavours to throw the odium of the War from himself upon the Lord Arlington, he desir'd that Lord might be ask'd who was the Author of the Triple-Alliance? As if he understood himself to be so. The Lord Arlington coming afterwards, upon the like desire, into the same House [Page 6] of Commons, and answering some parts of the Duke's Speech, when he came to that Particular, He told them, he could easily answer that Question of the Duke's, by telling them, That the Author of that Alliance was Sir William Temple. This, I suppose gave the occasion for Reflections upon what had pass'd in the course of my former Ambassies in Holland, and at Aix; and His Majesty, and his Ministers, the resolution to send for me out of my private retreat, where I had passed two years (as I intended to do the rest of my Life) and to engage me in going over into Holland to make the separate Peace with that State.
The only difficulties that appeared in this Affair, were what the Confederates were like to make in accepting the King's Mediation, whose late engagements with [Page 39] France had made him thought very partial on that side. And the House of Austria finding that Crown now abandon'd by England, had too greedily swallow'd the hopes of a revenge upon them, to desire any sudden Treaty, till the Successes they expected in the War might at least make way for reducing France to the Terms of that at the Pyrenees. This, I suppose, gave some occasion for my being again design'd for this Ambassy, who was thought to have some credit with Spain as well as Holland from the Negotiations I had formerly run through at the Hague, Brussels and Aix la Chapelle, by which the remaining parts of Flanders had been sav'd out of the hands of France in the Year 1668.
[Page 45]My Ambassy extraordinary to Holland was declar'd in May, and my Dispatches finish'd at the Treasury as well as the Secretary's Office; so as I went away in July. My instructions were in general, To assure the States of His Majesty's Friendship, and firm Resolution to observe his Treaties with them; then to offer his Mediation in the present War, which both They, and almost all Christendom, were engag'd in; and after their acceptance of it, to endeavour it likewise with all their Allies; and, to that end, to engage the Offices and Intervention of the States. But immediately after my arrival at the Hague, to repair to the Prince of Orange, give him part of His Majesties Intentions in all this Affair, and assurance of his kindness, and engage His Highness, as far as could be, to second His Majesty's desires, in promoting a General Peace, wherein the Vnited Provinces [Page 46] seem'd to have the greatest Interest.
With the Prince of Orange, return'd most of the General Officers to the Hague; and among the rest, old Prince Maurice of Nassau, who, as the Prince told me, had with the greatest industry that [Page 76] could be, sought all occasions of dying fairly at the Battel of Seneffe without succeeding, which had given him great regrets; and I did not wonder at it, considering his Age, of about Seventy six, and his long habits both of Gout and Stone. When he came to visit me upon his return, and before he went to his Government of Clevo, it came in my head to ask him an idle question, because I thought it not very likely for me to see him again, and I had a mind to know from his own mouth, the account of a common, but much credited Story, that I had heard so often from many others, of an old Parrot he had in Brasil, during his Government there, that spoke, and ask'd, and answer'd common questions like a reasonable creature; so that those of his Train there, generally concluded it to be Witchery or Possession; and one of his Chaplains, who liv'd long afterwards [Page 77] in Holland, would never from that time endure a Parrot, but said, They all had a Devil in them. I had heard many particulars of this story, and assever'd by people hard to be discredited, which made me ask Prince Maurice, What there was of it? He said, with his usual plainness, and dryness in talk, There was something true, but a great deal false, of what had been reported. I desir'd to know of him, What there was of the first? He told me short and coldly, That he had heard of such an old Parrot when he came to Brasil; and tho he believ'd nothing of it, and 'twas a good way off, yet he had so much curiosity as to send for it; That 'twas a very Great, and a very Old One; and when it came first into the Room where the Prince was, with a great many Dutch-men about him, it said presently, What a Company of White Men are here? They ask'd it, What he thought [Page 78] that Man was? pointing at the Prince. It answer'd, Some General or other. When they brought it close to him, he ask'd it, * D'ou venes, vous? It answer'd, De Marinnan. The Prince, A qui est es vous, The Parrot, A un Portugez. Prince, Que fais tula? Parrot, Je garde les Poulles. The Prince laugh'd, and said, Vous gardes les Poulles? The Parrot answered, Ouy, moy & je scay bien faire, and made the Chuck four or five times that people use to m [...]ke to Chickens when they call them. I set down the words of this worthy Dialogue in French, just as Prince Maurice said them to me. I ask'd him, In what Language the Parrot spoke? And he said, In Brasilian. I ask'd, Whether he understood [Page 79] Brasilian? He said, No; but he had taken care to have two Interpreters by him, one a Dutchman, that spoke Brasilian, and t'other a Brasilian that spoke Dutch; That he as'k them separately and privately, and both of them agreed in telling him just the same thing that the Parrot said. I could not but tell this odd story, because it is so much out of the way, and from the first hand, and what may pass for a good one; for I dare say this Prince, at least, believed himself in all he told me, having ever pass'd for a very honest and pious Man. I leave it to Naturalists to reason, and to other men to believe as they please upon it; however, it is not, perhaps, amiss to relieve or enliven a busie Scene sometimes with such digressions, whether to the purpose or no. 2ff7e9595c
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